elastin and Lung-Diseases

Elastin is expressed in most tissues that require elastic recoil. The protein first appeared coincident with the closed circulatory system, and was critical for the evolutionary success of the vertebrate lineage. Elastin is expressed by multiple cell types in the lung, including mesothelial cells in the pleura, smooth muscle cells in airways and blood vessels, endothelial cells, and interstitial fibroblasts. This highly crosslinked protein associates with fibrillin-containing microfibrils to form the elastic fiber, which is the physiological structure that functions in the extracellular matrix. Elastic fibers can be woven into many different shapes depending on the mechanical needs of the tissue. In large pulmonary vessels, for example, elastin forms continuous sheets, or lamellae, that separate smooth muscle layers. Outside of the vasculature, elastic fibers form an extensive fiber network that originates in the central bronchi and inserts into the distal airspaces and visceral pleura. The fibrous cables form a looping system that encircle the alveolar ducts and terminal air spaces and ensures that applied force is transmitted equally to all parts of the lung. Normal lung function depends on proper secretion and assembly of elastin, and either inhibition of elastin fiber assembly or degradation of existing elastin results in lung dysfunction and disease.

Topics: Animals; Elastin; Extracellular Matrix; Humans; Lung; Lung Diseases

Chemoattractant properties of matrix proteins, like collagen and elastin, for neutrophils and monocytes in vitro have long been recognized. This activity often resides in fragments of these proteins. These peptides may play a role in diseases of the lung matrix, such as chronic obstructive pulmonary disease. Recent advances include the elucidation of the structure of chemotactic collagen fragments and the demonstration that their activity may reside in a structural relatedness to CXC chemokines. Collagen and elastin fragments have been demonstrated to have a role in in vivo lung pathophysiology and have been quantified in patients with chronic lung diseases where they may activate autoimmune pathways. Elucidation of these pathways may provide novel biomarkers and therapeutic targets for chronic lung diseases.

Topics: Animals; Chemokines, CXC; Chemotactic Factors; Collagen; Elastin; Extracellular Matrix Proteins; Humans; Inflammation; Lung; Lung Diseases; Matrix Metalloproteinase 9; Oligopeptides; Peptide Fragments; Peptide Hydrolases; Pulmonary Disease, Chronic Obstructive

Topics: Animals; Biological Factors; Bronchi; Child; Disease Models, Animal; Elastin; Extracellular Matrix; Humans; Hypoxia; Infant; Infant, Newborn; Infant, Premature, Diseases; Lung; Lung Diseases; Lung Transplantation; Mechanotransduction, Cellular; Oxygen; Pluripotent Stem Cells; Pulmonary Alveoli; Pulmonary Artery; Respiration; Species Specificity

Elastic fibres are an important component of connective tissue. They are composed of two elements: protein-elastin and microfibrils. Tissue rich in elastin include: aorta and major vessels, lungs, ligaments, tendons and skin. Elastases are a group of enzymes, which are able to degrade elastin. They are liberated from different cells including granulocytes, monocytes, lymphocytes, skin fibroblasts, cancer cells and others. The product of elastin degradation is known as elastin-derived peptides (EDP) and is a marker of elastolysis. Elastin-derived peptides are thought to act on elastin-laminin receptor (ELR), which is located on membrane of fibroblasts, granulocytes, lymphocytes, monocytes and' cancer cells. An increased elastin turnover can occur in several disorders, including malignancies, but its role is not well known. There are a group of inherited diseases affecting elastic fibres e.g. Marfan syndrome. It seems, that elastin degradation plays an important role in pathogenesis of some cardiovascular and pulmonary diseases. An enhanced elastolytic activity in malignancies is also observed. The data are rather sparse and above all concern lung and breast cancer. A trial estimating the role of elastin turnover in patients with hematologic malignancies, who underwent bone marrow transplantation, is now conducting in our department and preliminary results are promising.

Topics: Autoimmune Diseases; Cardiovascular Diseases; Elastic Tissue; Elastin; Humans; Lung Diseases; Neoplasms; Peptide Fragments; Receptors, Laminin; Risk Factors

Topics: Elastin; Gene Expression Regulation; Humans; Lung; Lung Diseases; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor beta; Tropoelastin

Mononuclear phagocytes have the capacity to produce an array of MMPs. Several of these proteinases are capable of degrading insoluble elastin, an important component for the structural stability of the lung. Matrilysin is a low molecular weight proteinase with a broad substrate specificity produced at highest levels in in vitro differentiated monocytes. The 92-kD gelatinase is a major product of human alveolar macrophages that is also an elastase. The most newly described member of the MMP family is human macrophage metalloelastase. This enzyme is also expressed in alveolar macrophages derived from cigarette smokers. Determining the contribution of these and other elastolytic proteinases to the pathogenesis of emphysema is a focus of ongoing research.

Topics: Animals; Elastin; Extracellular Matrix; Humans; Lung Diseases; Macrophages, Alveolar; Matrix Metalloproteinase 7; Metalloendopeptidases; Monocytes; Pancreatic Elastase

Topics: Animals; Cell Adhesion Molecules; Cell Communication; Collagen; Cytoskeleton; Elastin; Extracellular Matrix; Humans; Lung; Lung Diseases; Proteoglycans

The important role that elastin plays in the development and proper function of lung has long been recognized. Also, the intimate connection between pulmonary emphysema and the destruction of alveolar elastin has been well established. Understanding the mechanisms regulating pulmonary elastin synthesis is crucial to fully understanding these normal and pathological processes. In this article, we review recent literature on elastin structure, the elastin gene and its multiple RNA transcripts, and the different tropoelastin isoforms that are translated from these mRNAs. The similarity of lung and aortic elastin and the cellular origin of lung elastin are also discussed. We next examine the few studies addressing regulation of elastin expression during lung development, maturation, and aging. The search for modulators of pulmonary elastogenesis, which has yielded mostly negative results, is then reviewed. Finally, we present a cell culture model that has been developed to study the molecular basis of lung injury in pulmonary emphysema.

Topics: Aging; Amino Acid Sequence; Animals; Elastin; Genes; Homeostasis; Humans; Lung; Lung Diseases; Molecular Sequence Data; Transcription, Genetic

Various elastases classes normally reside in alveolar structure and are liable to degrade the elastin as well as the other macromolecular components of pulmonary extracellular matrix (collagen, proteoglycans, fibronectin...), during lung injury. The most are the polymorphonuclear or monocyte serine elastase and the macrophage metallo and cysteine elastases. Metalloelastase may also arise from pathogenic bacteria as Pseudomonas aeruginosa. In another part proteases elastase-type from fibroblasts, endothelial cells or alveolar macrophages might to be involved into the remodelling of lung connective tissue or pulmonary cells differentiation and activation. The regulation of elastolytic activities, is supported both by activators (as plasminogen activator...) and inhibitors (alpha 1 Pi, 2M, BrI, TIMP, bacterial inhibitors...). These inhibitors are mostly generated in situ from macrophages, monocytes or polymorphonuclear cells so allowing to control fast local elastolytic activity. Since alveolar macrophage can internalize leucocyte elastase, synthetize metalloelastases, and secrete their inhibitors and activators, it plays a complex role in the lung defense and during various pulmonary pathogenesis. In conclusion, the lung response to bacterial or viral infections, the intensity of alveolitis, the nature and the gravity of emphysematous or fibrotic lung lesions, as well as the tumour growth or metastatic pulmonary invasion may depend upon the lung elastolytic activities.

Topics: Animals; Elastin; Endopeptidases; Humans; Lung; Lung Diseases; Pancreatic Elastase; Pulmonary Alveoli; Pulmonary Emphysema; Pulmonary Fibrosis

Topics: Animals; Disease Models, Animal; Elastin; Humans; Lung; Lung Diseases; Pancreatic Elastase

The matrix of the lung parenchyma is composed predominantly of collagen, elastin, glycosaminoglycans, and fibronectin. This presentation focuses on the newer insights into injury and repair of lung elastin and glycosaminoglycans. Elastin and glycosaminoglycans respond in characteristic patterns to destructive and proliferative forms of lung injury. Elastin degradation induced by elastases induces a prompt and marked response by elastin resynthesis in situ. The signal for the stimulus remains unknown and deserves to be understood. The measurement of elastin peptides in plasma, urine, or bronchoalveolar lavage fluid can provide an objective index of elastin degradation in disease. Elastin depletion may be augmented by factors that interfere with elastin resynthesis such as exposure to tobacco smoke. Glycosaminoglycans participate in similar fashion in many different forms of lung injury as an early response to injury, which may then determine the subsequent cellular processes of repair. Studies of injury and repair in organ systems, other than the lung, suggest a general role for glycosaminoglycans in interstitial tissue and repair. The mediators that alter matrix chemical structure and function could provide powerful instruments for controlling the process of tissue injury and repair in the lung.

Topics: Airway Resistance; Animals; Chemical Phenomena; Chemistry; Collagen; Elastin; Endotoxins; Escherichia coli; Fibronectins; Glycosaminoglycans; Humans; Lung; Lung Compliance; Lung Diseases; Lung Diseases, Obstructive; Pancreatic Elastase; Pressure; Protease Inhibitors; Pulmonary Emphysema; Regeneration

Topics: Amines; Angiotensin II; Animals; Bradykinin; Connective Tissue; Elastin; Glucose; Humans; Lung; Lung Diseases; Phospholipids; Procollagen; Prostaglandins; Proteins; Pulmonary Alveolar Proteinosis; Pulmonary Surfactants; Rats

Topics: Animals; Elastin; Histocytochemistry; Humans; Hyaline Membrane Disease; Infant, Newborn; Infant, Newborn, Diseases; Lung; Lung Diseases; Pneumonia; Pulmonary Surfactants; Respiratory Therapy

Topics: Adult; Age Factors; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Alpha-Globulins; Animals; Antigen-Antibody Reactions; Cadmium; Collagen; Elastin; Environmental Exposure; Humans; Infant; Leukocytes; Lung; Lung Diseases; Macrophages; Microbial Collagenase; Nitrogen Dioxide; Ozone; Pancreatic Elastase; Peptide Hydrolases; Pulmonary Alveoli; Pulmonary Edema; Pulmonary Emphysema; Smoking

The lung Extracellular Matrix (ECM) contains a considerable part of the parenchymal cells. It contains three essential components: elastin and collagen within a proteoglycan (PG) viscoelastic network. Elastin provides the lung's elasticity property, a necessity for normal breathing, while collagen prepares structural support and strength, and PGs give stability and cushioning within tissue loading. Bacterial and viral respiratory diseases are dependent on changes in the ECM ingredients, which result in an alteration of the lung tissue strength.. In the present study, this variation was investigated by changing the volume ratio of the ECM ingredients in the viscoelastic model.. As a result, the relaxation curves continuously declined by reducing the volume ratios of elastin, collagen, and PGs; subsequently, the lung stiffness decreased. Also, the Standard Linear Solid (SLS) model-based results demonstrated excellent accordance with empirical data with only minor deviations. The resting relaxation modulus and the creep modulus for the ECM tissue were 51 kPa and approximately 0.02 kPa, respectively, and the maximum total modulus of elasticity reached 121 kPa.. Moreover, this model demonstrates individual alveolar mechanical behaviours and adds another pathway to the generalized Kelvin-Voigt and Maxwell models in predicting the progress of lung diseases.

Topics: Collagen; Elasticity; Elastin; Humans; Lung; Lung Diseases; Stress, Mechanical

Exercise-induced pulmonary hemorrhage (EIPH) is a common condition of Thoroughbred racehorses that is usually responsible for reduced performance, while exercise-associated fatal pulmonary hemorrhage (EAFPH) is characterized by severe pulmonary bleeding of unknown pathogenesis resulting in sudden death during strenuous exercise. The aim of the study was to characterize and compare anamnestic data together with pulmonary gross, histologic, and ultrastructural findings in racehorses with EIPH (n = 10), EAFPH (n = 10), and control horses (n = 5). No differences in anamnesis were identified between the 3 groups. Grossly cranial lobe reddening and edema scores were significantly more prevalent and severe in the EAFPH group compared with the EIPH and control groups. Histologically, hemorrhage scores were higher in the EAFPH group, while hemosiderophages, iron encrustations of collagen and elastin fibers, and vascular remodeling scores were significantly higher in EIPH group compared with the EAFPH and control groups. In all groups, caudal lung locations exhibited a significantly higher score for vascular remodeling, hemosiderophage accumulation, iron encrustation, and type II pneumocyte hyperplasia when compared with cranial, dorsal, and ventral locations. Ultrastructural analysis of perivascular collagen showed fibrils with significantly larger diameters in the EAFPH group compared with the EIPH group but not compared with the control group. This study demonstrates that lungs of horses that experienced EAFPH show significantly less vascular remodeling and other long-term pulmonary abnormalities that characterize horses with EIPH.

Topics: Animals; Collagen; Elastin; Hemorrhage; Horse Diseases; Horses; Iron; Lung; Lung Diseases; Physical Conditioning, Animal; Vascular Remodeling

Elastin is a unique protein providing deformability and resilience to dynamic tissues, such as arteries and lungs. It is an absolute basic requirement for circulation and respiration. Elastin can be degraded by elastases and has a high calcium affinity. Elastin calcification and elastin degradation are two pathological processes that impair elastin's functioning. Furthermore, elastin degradation can be associated to elastin calcification. Matrix Gla Protein (MGP) is probably the most potent natural inhibitor of elastin calcification and requires vitamin K for its activation. Measuring circulating levels of inactive MGP (dp-ucMGP) is a frequently used method to assess vitamin K status. Dp-ucMGP reflects the burden of vitamin K-dependent proteins that have not been activated by vitamin K and could therefore best be regarded as a biomarker of a vitamin K deficit. Dp-ucMGP levels decrease after vitamin K supplementation. Since the amino acids desmosine and isodesmosine (DES) are unique to crosslinked elastin fibers, systemic elastin degradation can be assessed with the plasma DES assay. Recently, we discovered a strong correlation between plasma dp-ucMGP and plasma DES levels in both patients with chronic obstructive pulmonary disease (COPD) and controls. The 'Vitamin K deficit and elastolysis theory' posits that elastin degradation causes a rise in the vitamin K deficit and implies that vitamin K supplementation could be preventing elastin degradation. If this hypothesis holds true and is universally found in every state and condition, it will have an unprecedented impact on the management of every single pulmonary disease characterized by accelerated elastin degradation, such as alpha-1 antitrypsin deficiency, bronchiectasis, COPD and cystic fibrosis. Theoretically, a plasma dp-ucMGP concentration of zero would be associated with a near-complete standstill of elastin degradation and disease progression in patients with any of these debilitating conditions.

Topics: alpha 1-Antitrypsin; Biomarkers; Calcium; Calcium-Binding Proteins; Desmosine; Elasticity; Elastin; Extracellular Matrix Proteins; Humans; Isodesmosine; Lung Diseases; Matrix Gla Protein; Models, Biological; Vitamin K; Vitamin K Deficiency

Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the quantification of MMP-7 generated elastin fragments (ELM7) was therefore developed to investigate MMP-7 derived elastin degradation in pulmonary disorders such as idiopathic pulmonary fibrosis (IPF) and lung cancer.. Monoclonal antibodies (mABs) were raised against eight carefully selected MMP-7 cleavage sites on elastin. After characterisation and validation of the mABs, one mAB targeting the ELM7 fragment was chosen. ELM7 fragment levels were assessed in serum samples from patients diagnosed with IPF (n=123, baseline samples, CTgov reg. NCT00786201), and lung cancer (n=40) and compared with age- and sex-matched controls.. The ELM7 assay was specific towards in vitro MMP-7 degraded elastin and the ELM7 neoepitope but not towards other MMP-7 derived elastin fragments. Serum ELM7 levels were significantly increased in IPF (113%, p<0.0001) and lung cancer (96%, p<0.0001) compared to matched controls.. MMP-7-generated elastin fragments can be quantified in serum and may reflect pathological lung tissue turnover in several important lung diseases.

Topics: Aged; Animals; Case-Control Studies; Elastin; Female; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases; Lung Neoplasms; Male; Matrix Metalloproteinase 7; Mice; Mice, Inbred BALB C; Middle Aged; Proteolysis

Elastic fibres are critical connective tissue components providing elasticity and resilience to skin and other tissues. These fibres are composed of elastin and a number of elastin-associated microfibrillar proteins that assemble in a complex fibre network in a multi-step process. Multiple cellular processes, including mitochondrial function, specific molecules in the secretory pathways and temporally and spatially ordered production of elastic fibre components, are required for the biogenesis of functional elastic fibres. Abnormalities in these processes can lead to loss of functional elastic fibres manifesting phenotypically as a skin disease. The paradigm of elastic fibre diseases affecting the skin is cutis laxa, a clinically and genetically heterogeneous group of disorders characterized by loose and sagging skin, frequently associated with extracutaneous manifestations in the lungs and the arterial blood vessels. The complexity of cutis laxa is emphasized by the fact that as many as 10 distinct genes can harbour mutations in this and related disorders. Understanding of the pathomechanistic pathways involved in perturbed elastic fibre assembly in cutis laxa provides information potentially helpful for the development of molecular strategies towards treatment of these, currently intractable, diseases.

Topics: Arteries; Chromosomes, Human, X; Cutis Laxa; Elastic Tissue; Elastin; Genes, Recessive; Humans; Lung Diseases; Microfibrils; Mitochondria; Mutation; Phenotype; Skin

Liberation of elastin peptides from damaged lung may be a mechanism of autoimmune lung disease. Citrullination, and anti-citrullinated protein antibody formation occurs in smokers, but the role of smoking in autoantibody generation relevant to pulmonary disease is unclear. Anti-elastin, anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies were measured in 257 subjects with α₁-antitrypsin deficiency (AATD), 113 subjects with usual chronic obstructive pulmonary disease (COPD) and 22 healthy nonsmokers. Levels were compared between groups, against phenotypic features and against smoke exposure. Anti-elastin antibodies were higher in controls relative to AATD (p = 0.008) and usual COPD (p < 0.00001), and in AATD relative to usual COPD (p < 0.00001). Anti-elastin levels showed a threshold at 10 pack-yrs, being higher in those who had smoked less (p = 0.004). No relationships between antibody levels and clinical phenotype were seen after adjustment for smoke exposure. Anti-CCP antibodies were higher in usual COPD than AATD (p = 0.002) but the relationship to smoke exposure was less clear. Smoke exposure is the main determinant of anti-elastin antibody levels, which fall after 10 pack-yrs. Local antibody complexes may be a better measure of elastin directed autoimmunity than circulating levels.

Topics: Adult; Aged; alpha 1-Antitrypsin Deficiency; Autoimmune Diseases; Elastin; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Middle Aged; Phenotype; Pulmonary Disease, Chronic Obstructive; Risk; Smoking; Time Factors

Neonatal chronic lung disease is characterized by failed formation of alveoli and capillaries, and excessive deposition of matrix elastin, which are linked to lengthy mechanical ventilation (MV) with O(2)-rich gas. Vitamin A supplementation has improved respiratory outcome of premature infants, but there is little information about the structural and molecular manifestations in the lung that occur with vitamin A treatment. We hypothesized that vitamin A supplementation during prolonged MV, without confounding by antenatal steroid treatment, would improve alveolar secondary septation, decrease thickness of the mesenchymal tissue cores between distal air space walls, and increase alveolar capillary growth. We further hypothesized that these structural advancements would be associated with modulated expression of tropoelastin and deposition of matrix elastin, phosphorylated Smad2 (pSmad2), cleaved caspase 3, proliferating cell nuclear antigen (PCNA), VEGF, VEGF-R2, and midkine in the parenchyma of the immature lung. Eight preterm lambs (125 days' gestation, term approximately 150 days) were managed by MV for 3 wk: four were treated with daily intramuscular Aquasol A (vitamin A), 5,000 IU/kg, starting at birth; four received vehicle alone. Postmortem lung assays included quantitative RT-PCR and in situ hybridization, immunoblot and immunohistochemistry, and morphometry and stereology. Daily vitamin A supplementation increased alveolar secondary septation, decreased thickness of the mesenchymal tissue cores between the distal air space walls, and increased alveolar capillary growth. Associated molecular changes were less tropoelastin mRNA expression, matrix elastin deposition, pSmad2, and PCNA protein localization in the mesenchymal tissue core of the distal air space walls. On the other hand, mRNA expression and protein abundance of VEGF, VEGF-R2, midkine, and cleaved caspase 3 were increased. We conclude that vitamin A treatment partially improves lung development in chronically ventilated preterm neonates by modulating expression of tropoelastin, deposition of elastin, and expression of vascular growth factors.

Topics: Animals; Animals, Newborn; Chronic Disease; Dietary Supplements; Elastin; Female; Gestational Age; Lung; Lung Diseases; Pregnancy; Premature Birth; Pulmonary Alveoli; Pulmonary Gas Exchange; Respiration, Artificial; Sheep; Tropoelastin; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vitamin A; Vitamins

In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 microm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.

Topics: Aging; Animals; Animals, Newborn; Arsenic; Collagen; Dose-Response Relationship, Drug; Elastin; Female; Gene Expression Regulation, Developmental; Lung; Lung Diseases; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth; Pregnancy; Prenatal Exposure Delayed Effects

Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis.. We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero.. Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days.. Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV.. Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.

Topics: Animals; Cell Proliferation; Elastin; Female; Fetal Diseases; Fetal Organ Maturity; Fetus; Lipopolysaccharides; Lung; Lung Compliance; Lung Diseases; Pulmonary Surfactant-Associated Protein B; Sheep

Cystic lung light chain deposition disease (CL-LCDD) is a recently described rare disorder characterised by numerous cysts and diffuse monoclonal nonamyloid light chain deposits surrounded by macrophagic giant cells. The mechanisms responsible for cyst development remain unknown. The objectives of the present study were to analyse the major components of the pulmonary extracellular matrix in CL-LCDD and to determine the influence of metalloproteinases (MMPs) by comparison with other cystic lung disorders. A virtually complete degradation of the elastic network was found in CL-LCDD. To a lesser degree, loss of fibrillar and basement membrane collagens was also observed. Macrophagic giant cells expressed MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14 and in situ zymography highlighted a strong gelatinolytic activity. As in CL-LCDD, cystic lesions in Langerhans' cell histiocytosis (LCH) and lymphangioleiomyomatosis (LAM) were characterised by the lack of elastic fibres. Similarly, MMP were expressed in CL-LCDD and LCH but the labelled cells were different. In contrast, few MMPs were detected in LAM. In conclusion, elastolysis is common to cystic lung light chain deposition disease and other cystic lung disorders, suggesting its implication in cyst formation. Moreover, in cystic lung light chain deposition disease, a role of metalloproteinases in elastolysis is strongly indicated by the metalloproteinase expression and activity pattern.

Topics: Adult; Cysts; Elastin; Extracellular Matrix; Female; Histiocytosis, Langerhans-Cell; Humans; Immunohistochemistry; Lung; Lung Diseases; Lung Transplantation; Lymphangioleiomyomatosis; Macrophages; Male

Pulmonary injury is associated with the disruption of alveologenesis in the developing lung and causes bronchopulmonary dysplasia (BPD) in prematurely born infants. Transforming growth factor (TGF)-beta is an important regulator of cellular differentiation and early lung development, and its levels are increased in newborn lung injury. Although overexpression of TGF-beta in the lungs of newborn animals causes pathological features that are consistent with BPD, the role of endogenous TGF-beta in the inhibition of the terminal stage of lung development is incompletely understood. In this investigation, the hypothesis that O(2)-induced injury of the maturing lung is associated with TGF-beta-mediated disruption of alveologenesis and microvascular development was tested using a murine model of BPD. Here we report that treatment of developing mouse lungs with TGF-beta-neutralizing antibodies attenuates the increase in pulmonary cell phospho-Smad2 nuclear localization, which is indicative of augmented TGF-beta signaling, associated with pulmonary injury induced by chronic inhalation of 85% oxygen. Importantly, the neutralization of the abnormal TGF-beta activity improves quantitative morphometric indicators of alveologenesis, extracellular matrix assembly, and microvascular development in the injured developing lung. Furthermore, exposure to anti-TGF-beta antibodies is associated with improved somatic growth in hyperoxic mouse pups and not with an increase in pulmonary inflammation. These studies indicate that excessive pulmonary TGF-beta signaling in the injured newborn lung has an important role in the disruption of the terminal stage of lung development. In addition, they suggest that anti-TGF-beta antibodies may be an effective therapy for preventing some important developmental diseases of the newborn lung.

Topics: Animals; Animals, Newborn; Antibodies; Cell Nucleus; Elastin; Female; Hyperoxia; Lung Diseases; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Neutralization Tests; Phosphoproteins; Protein Isoforms; Protein Transport; Pulmonary Alveoli; Smad2 Protein; Transforming Growth Factor beta

Elastin fibres in sputum have been described as a more sensitive marker of pulmonary necrosis than plain chest X-rays. This study aimed to determine the prevalence of elastin fibres using non-directed non-protected mini-bronchoalveolar lavage (BM-BAL) in mechanically ventilated patients in the intensive care unit. Patients admitted to the general intensive care unit of a tertiary referral hospital requiring more than 48 hours of mechanical ventilation had surveillance BM-BAL performed on admission and were then examined weekly using potassium hydroxide wet preparations for the presence of elastin fibres. All positive and a random selection of 16 negative preparations from patients with acute respiratory distress syndrome or pneumonia were fixed and examined using Weigert's staining method for elastin. Of 412 patients enrolled, 130 (32%) had pneumonia on admission, 50 (12%) developed 58 episodes of ventilator-associated pneumonia and acute respiratory distress syndrome was diagnosed in 86 patients (21%). No chest X-ray showed cavitating infiltrates. Of 985 specimens examined, only seven had elastin fibres. Elastin fibres are uncommonly found using BM-BAL in general screening, acute respiratory distress syndrome or pneumonia in the intensive care unit, the incidence too low to be a useful indicator of pulmonary necrosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Elastin; Female; Humans; Intensive Care Units; Lung Diseases; Male; Middle Aged; Necrosis; Pneumonia; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Distress Syndrome

Topics: Collagen; Disease Progression; Elastin; Humans; Lung Diseases; Models, Biological; Nonlinear Dynamics

The involvement of genes controlling embryonic processes in the etiology of diseases often escapes attention because of the focus given to their inherent developmental role. Hoxa5 belongs to the Hox gene family encoding transcription factors known for their role in skeletal patterning. Hoxa5 is required for embryonic respiratory tract morphogenesis. We now show that the loss of Hoxa5 function has severe repercussions on postnatal lung development. Hoxa5-/- lungs present an emphysema-like morphology because of impaired alveogenesis. Chronic inflammation characteristics, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells, were also observed. Altered cell specification during lung morphogenesis triggered goblet cell anomalies. In addition, the defective motility of alveolar myofibroblast precursors in the embryonic lung led to the mispositioning of the alveolar myofibroblasts and to abnormal elastin deposition postnatally. Both goblet cell hyperplasia and elastic fiber abnormalities contributed to the chronic physiopathological features of Hoxa5-/- lungs. They constituted an attractive stimulus to recruit activated macrophages that in turn generated a positive feedback loop that perpetuated macrophage accumulation in the lung. The present work corroborates the notion that altered Hox gene expression may predispose to lung pathologies.

Topics: Animals; Apoptosis; Cell Proliferation; Elastin; Fibroblasts; Homeodomain Proteins; Lung; Lung Diseases; Mice; Mice, Mutant Strains; Mutation; Organ Size; Organogenesis; Phosphoproteins; Pulmonary Alveoli; Stem Cells; Transcription Factors

Nitric oxide (NO) serves multiple functions in the developing lung, and pulmonary NO production is decreased in a baboon model of chronic lung disease (CLD) after premature birth at 125 days (d) gestation (term = 185d). To determine whether postnatal NO administration alters the genesis of CLD, the effects of inhaled NO (iNO, 5 ppm) were assessed in the baboon model over 14d. iNO caused a decrease in pulmonary artery pressure in the first 2d and a greater rate of spontaneous closure of the ductus arteriosus, and lung compliance was greater and expiratory resistance was improved during the first week. With iNO, postmortem pressure-volume curves were shifted upward, lung DNA content and cell proliferation were increased, and lung growth was preserved to equal that which occurs during the same period in utero. In addition, the excessive elastin deposition characteristic of CLD was normalized by iNO, and there was evidence of stimulation of secondary crest development. Thus, in the baboon model of CLD, iNO improves early pulmonary function and alters lung growth and extracellular matrix deposition. As such, NO biosynthetic pathway dysfunction may contribute to the pathogenesis of CLD.

Topics: Administration, Inhalation; Animals; Animals, Newborn; Bronchodilator Agents; Chronic Disease; Elastin; Hemodynamics; Image Processing, Computer-Assisted; Lung; Lung Diseases; Nitric Oxide; Organ Size; Papio; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Circulation

Matrix metalloproteinases (MMPs) are degradative enzymes, which act to remodel tissue. Their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the degradation/inhibition activities has been associated with many diseases, including sepsis. We have previously shown that TIMP-3 knockout animals develop spontaneous, progressive air space enlargement. The objectives of this study were to determine the effects of a septic lung stress induced by cecal ligation and perforation (CLP) on lung function, structure, pulmonary surfactant, and inflammation in TIMP-3 null mice. Knockout and wild-type animals were randomized to either sham or CLP surgery, allowed to recover for 6 h, and then euthanized. TIMP-3 null animals exposed to sham surgery had a significant increase in lung compliance when compared with sham wild-type mice. Additionally, the TIMP-3 knockout mice showed a significant increase in compliance following CLP. Rapid compliance changes were accompanied by significantly decreased collagen and fibronectin levels and increased gelatinase (MMP-2 and -9) abundance and activation. Additionally, in situ zymography showed increased airway-associated gelatinase activity in the knockout animals enhanced following CLP. In conclusion, exposing TIMP-3 null animals to sepsis rapidly enhances the phenotypic abnormalities of these mice, due to increased MMP activity induced by CLP.

Topics: Animals; Collagen; Elastin; Female; Fibronectins; Immunohistochemistry; Interleukin-6; Lung Compliance; Lung Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Alveoli; Pulmonary Surfactants; Sepsis; Tissue Inhibitor of Metalloproteinase-3; Tumor Necrosis Factor-alpha

A neutrophil elastase inhibitor FR901277 was examined for its inhibitory effect on degradation of natural substrate elastin in vitro, and on acute inflammatory states and pulmonary emphysema in vivo.. Elastin-congo red was used as a substrate for elastin degradation assay. Paw edema in male C57BL mice (6 weeks old) and pulmonary hemorrhage in female golden hamsters (5 weeks old) were induced by topical injection of human neutrophil elastase (HNE). Pulmonary emphysema in male golden Syrian hamsters (10 weeks old) was provoked by intratracheal instillation of porcine pancreatic elastase. In all in vivo experiments. FR901277 was administered prior to elastase treatment.. Elastin degradation by HNE was monitored spectrophotometrically with elastin-congo red. Foot swelling was measured by calipers. Pulmonary hemorrhage was assessed by hemoglobin concentration in bronchoalveolar lavage fluid. As emphysematous parameters, quasi-static lung compliance and vital capacity were measured.. FR901277 inhibited HNE-induced elastin degradation. Systemic treatment with FR901277 significantly inhibited paw edema and pulmonary hemorrhage. Intratracheal treatment with FR901277 significantly ameliorated changes in pulmonary function.. These results suggest that FR901277 inhibits the elastase activity potently both in vitro and in vivo, and that elastase may play a role at least in part in pathogenesis of pulmonary emphysema.

Topics: Amides; Animals; Cricetinae; Edema; Elastin; Enzyme Inhibitors; Female; Hemorrhage; Humans; Inflammation; Leukocyte Elastase; Lung Diseases; Male; Mesocricetus; Mice; Mice, Inbred C57BL; Pancreatic Elastase; Pulmonary Emphysema; Swine

In this communication we offer data to suggest that the zebrafish swimbladder may provide a simple model of elastin injury and repair which is amenable to genetic analysis and pertinent to lung physiology. In situ hybridization of zebrafish embryos illustrated that elastin gene expression is evident in the developing gut tract prior to swimbladder morphogenesis. Northern blot analysis demonstrated that the major zebrafish elastin mRNA is 2.0 kb which is significantly smaller than its higher vertebrate counterpart. Amino acid analysis of alkali-resistant protein from the anterior chamber of the adult zebrafish swimbladder showed a composition similar to higher vertebrate elastins including significant amounts of desmosine crosslinks. Electron microscopic investigations of the swimbladder wall indicate a simple structure with an inner layer of elastin fibers. Elastase delivery to the swimbladder in vitro resulted in significant fragmentation of elastin in the anterior chamber providing an environment for studying elastin repair within the tissue.

Topics: Air Sacs; Amino Acids; Animals; Blotting, Northern; Elastin; Gene Expression; In Situ Hybridization; Intestines; Lung Diseases; Models, Biological; Morphogenesis; Pancreatic Elastase; RNA; RNA, Messenger; Wound Healing; Zebrafish

In the normal, healthy lung, elastin production is restricted to periods of development and growth. However, elastin expression in the adult lung has been observed in some forms of pulmonary injury, including pulmonary fibrosis. Here, we report that elastin production is significantly increased within precise interstitial compartments of the lung in an experimental model of granulomatous lung disease. An increase in the number and volume of elastic fibers within the alveolar walls was apparent on histological examination of Verhoeff-van Gieson-stained sections of silicotic rat lungs. Quantitation of mature elastin cross-links indicated that silicosis was accompanied by a 17-fold increase in lung elastin content when compared with values from saline-treated controls. In situ hybridization for tropoelastin mRNA revealed that elastin production was absent from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips, where a high density of elastic fibers is seen in the normal lung. Immunohistochemistry indicated tropoelastin was being expressed by alpha-smooth muscle actin-containing cells. Transforming growth factor-beta was immunolocalized to granulomatous regions of the silicotic lung but was absent from regions showing increased tropoelastin expression. These data indicate that the reinitiation of tropoelastin gene expression is associated with granulomatous lung disease, and this expression leads to the aberrant accumulation of mature elastin in the lung.

Topics: Actins; Animals; Elastin; Gene Expression; Granuloma; Lung Diseases; Male; Muscle, Smooth; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Silicosis; Solubility; Tissue Distribution; Transforming Growth Factor beta; Tropoelastin

Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260-330 g) were fed either an AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH2 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either O3 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as O3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH2 has minimal influence on other compensatory mechanisms developed over time.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Collagen; Desmosine; Elastin; Female; Guinea Pigs; Hydroxyproline; Lung Diseases; Lung Volume Measurements; Organ Size; Ozone; Procollagen-Proline Dioxygenase; Respiratory Function Tests; Tissue Fixation

Current concepts of pathomechanisms leading to acquired emphysema suggest that alveolar macrophages (AM) activated by cigarette smoking may cause an elastase/antielastase imbalance localized to the microenvironment formed by phagocytes and lung tissue. A functional cell assay was used to evaluate the cell-associated elastinolytic activity of AM. AM were obtained by bronchoalveolar lavage from patients with emphysema and from patients with non obstructive chronic pulmonary diseases (non-COPD) and cultured under serum-free conditions in direct contact with 3H-labeled elastin particles. Elastinolytic activity was calculated from the released radioactivity in culture supernatants and expressed as micrograms of 3H-elastin degraded x 10(-5) AM x 72 h-1. AM of patients with emphysema had significantly higher elastinolytic activity compared to that of non-COPD patients (median: 10.8 versus 4.1 micrograms; P < 0.01). Further differentiation of patients revealed the lowest median activity in sarcoidosis (2.3 micrograms). In respect to smoking habits there was a major difference between smokers with emphysema degraded more than twice the amount of elastin than smokers in the non-COPD group (median:11 versus 3.9 micrograms, P = 0.01). From these data we conclude that AM-derived elsatinolytic proteases may be involved in the destruction of lung elastin, which is thought to be the key event occurring in the pathogenesis of pulmonary emphysema.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Elastin; Female; Humans; Lung Diseases; Macrophages, Alveolar; Male; Middle Aged; Pancreatic Elastase; Pulmonary Emphysema; Respiratory Function Tests; Smoking

Inhibitors of human leukocyte elastase (HLE) may exert potent therapeutic effects on pulmonary emphysema, adult respiratory distress syndrome and other diseases involving tissue degradation. 7-(4-Chlorophenylsulfonyl-L-glutanyl)amino-5-methyl-2-isopro pylamino-4H-3,1- benzoxazin-4-one (TEI-5624) and 7-(4-chlorophenylsulfonyl-L-lysyl)amino-5-methyl-2- isopropylamino-4H-3,1-benzoxazin-4-one (TEI-6344), two derivatives of 5-methyl-4H-3,1-benzoxazin-4-one, showed strong and highly specific inhibition of human sputum elastase (HSE), which is equivalent to HLE, with Ki values of 6.91 and 16.3 nM, respectively. The selectivity of TEI-5624 for HSE vs. several proteinases ranged from 300-fold to 45,000-fold in favor of HSE. TEI-5624 and TEI-6344 also efficiently prevented degradation of insoluble elastin by stimulated polymorphonuclear leukocytes. The elastase inhibitory capacity of these compounds was not affected by treatment with stimulated polymorphonuclear leukocytes or Pseudomonas aeruginosa-origin elastase. When administered intratracheally to hamsters. TEI-5624 and TEI-6344 were eliminated from the lung with half-times of 85 and 240 min, respectively. In acute injury induced by intratracheal administration of HSE in hamsters, these compounds significantly suppressed pulmonary hemorrhage when administered intratracheally (1 mg/kg) either 30 or 240 min before challenge with HSE (1 mg/kg). HSE-induced emphysema in hamsters was also prevented by TEI-5624 (1 mg/kg) administered intratracheally 7 hr after HSE administration (1 mg/kg). These results suggest that TEI-5624 and TEI-6344 may be useful therapeutic agents for the treatment of HLE-mediated diseases.

Topics: Amino Acid Sequence; Animals; Benzoxazines; Binding Sites; Cells, Cultured; Cricetinae; Drug Stability; Elastin; Hemorrhage; Humans; Leukocyte Elastase; Lung Diseases; Male; Mesocricetus; Molecular Sequence Data; Oxazines; Oxidation-Reduction; Pancreatic Elastase; Sputum; Sulfonamides

The effect of maternal nicotine exposure (1 mg/kg body mass/d) on the lung elastic tissue of 1-day-old rat pups was investigated. The results show that maternal nicotine exposure resulted in a very low elastic tissue content in the lungs of these rat pups compared with those of the controls. This may interfere with normal lung development since elastic tissue is part of the lung connective tissue structure and is involved in the formation of alveoli. Impaired elastic synthesis may thus make the rat pups more susceptible to lung diseases such as emphysema.

Topics: Animals; Animals, Newborn; Elastic Tissue; Elastin; Female; Lung; Lung Diseases; Maternal-Fetal Exchange; Nicotine; Pregnancy; Rats; Rats, Inbred Strains

Human pulmonary hypoplasia was studied statistically and pathologically in a large series of autopsy cases. Multiple logistic regression analysis indicated five independent risk factors from 10 statistically significant factors for pulmonary hypoplasia: (1) hydrops fetalis; (2) renal anomalies; (3) hernia, including diaphragmatic hernia and omphalocele; (4) skeletal anomalies; and (5) abnormalities of amniotic fluid, such as oligohydramnios and polyhydramnios. The characteristics of pulmonary hypoplasia for each factor were defined by morphological, morphometric, and biochemical methods. All bronchiolar branching, acinar complexity, and acinar maturation were retarded in hypoplastic lungs with hydrops fetalis, renal anomalies, affected side of diaphragmatic hernia, omphalocele, and skeletal anomalies. Only acinar complexity and maturation were impaired in the lung with oligohydramnios due to prolonged rupture of membranes. The pathogenesis of pulmonary hypoplasias should be considered differently with each associated anomaly and time of impairment. While impairment in early gestational stage before 16 weeks' gestation results in both reduced bronchiolar branching and retarded acinar development, that, at late stage, influences only acinar development.

Topics: Amino Acids; Blood-Air Barrier; Body Weight; Bronchi; Elastin; Humans; Infant, Newborn; Lung; Lung Diseases; Microscopy, Electron; Microscopy, Electron, Scanning; Organ Size; Pulmonary Alveoli

Desmosine is an amino acid specific to elastin. Animal studies suggest that urinary desmosine (UD) represents endogenous elastin degradation. Therefore, UD has previously been used to investigate endogenous elastolysis, but was not elevated in subjects with chronic obstructive airways disease (COAD), although accelerated pulmonary elastolysis is thought to contribute to COAD. We have investigated whether this reflects large day-to-day and between-subject variation in UD and whether, in man, dietary desmosine contributes significantly to that in urine. Mean 24-hour UD output (over 5 consecutive days) from 10 asymptomatic subjects (5 males) was higher in males than females (77.4 +/- 9.6 and 40.2 +/- 5.0 nmol/24 hours, respectively; mean +/- SD, P less than .001), but not significantly different when expressed in terms of creatinine (micrograms desmosine/100 mg creatinine: males, 2.5 +/- 0.4; females, 3.1 +/- 0.8; mean +/- SD). The lowest between-subject variation was observed when the mean of 5 days' 24-hour UD values was analyzed on the basis of gender (coefficient of variation [CV], 12.5%); when gender was not considered, the least between-subject variation was found for the mean of 5 days' desmosine/creatinine analysis (CV, 24.5%). Approximately 1% of dietary desmosine (ingested as [3H]elastin and [3H] desmosine) was excreted in the urine within 24 hours, contributing approximately 15% of UD while on a normal diet. Although ingestion of a low elastin diet (less than 1/10 desmosine/24 hours than a normal diet) resulted in lower within-subject variation in 24-hour UD excretion (mean CV decreased from 31.5% to 20.2%), the between-subject CV and UD levels did not alter.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; alpha 1-Antitrypsin Deficiency; Desmosine; Diet; Elastin; Female; Humans; Injections, Intravenous; Lung Diseases; Male; Middle Aged; Reference Values

Recent evidence suggests that connective tissue breakdown in the human lung leading to airway obstruction and emphysema involves proteinases expressed by neutrophils and macrophages that traffic to the lungs in response to cigarette smoke. It remains unclear why only a small fraction of all cigarette smokers develop symptomatic airway obstruction. In this study, we examined indexes of inflammation and proteolytic activity in samples of bronchoalveolar lavage from young cigarette smokers and questioned whether there was any correlation between the extent of inflammation or enzymatic activity and lung function. A total of 125 apparently healthy community volunteers who currently smoked at least one pack per day were evaluated by spirometry. Seven subjects with a relatively low FEV1/FVC (% predicted) were identified and further studied by bronchoalveolar lavage. These were compared with a group of 10 smokers of similar age (mean age, 33 yr) and pack-years and higher FEV1/FVC (% predicted). Both groups showed increased accumulation of lung macrophages and neutrophils as compared to nonsmokers, but there were no differences in total cells or cellular differentials between the groups. Similarly, there were no differences in either alveolar fluid phase elastase, antielastase, and plasminogen activator (PA) activities or macrophage elastolytic activity between the groups. In contrast, there was a clear difference in macrophage plasminogen activator activity between the groups, cells from the group with a lower FEV1/FVC (% predicted) having a higher PA activity than that of macrophages from the group with higher FEV1/FVC (% predicted), i.e., 0.50 +/- 0.16 international urokinase units/10(6) cells versus 0.30 +/- 0.10 units/10(6) cells (p less than 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bronchoalveolar Lavage Fluid; Elastin; Forced Expiratory Volume; Forecasting; Humans; Inflammation; Lung; Lung Diseases; Macrophages; Middle Aged; Pancreatic Elastase; Plasminogen Activators; Pulmonary Alveoli; Respiratory Function Tests; Smoking; Vital Capacity

Severe airway lesions can result following exposure to various pathogens or toxic gases and can show a variety of pathologic lesions including necrotizing bronchitis, bronchiolitis and bronchiectasis. The purpose of this study was to develop a chronic airway lesion in the hamster, a species recognized for its lack of endogenous pulmonary disease. We have successfully adapted a technique of inducing rabbit airway lesions with nitric acid to the hamster lung and have characterized the morphologic, morphometric and biochemical features of the model. Following a transorotracheal instillation of 0.5% HNO3 in saline, Syrian golden hamsters showed during a 60-day study period a spectrum of airway changes including acute bronchitis, acute bronchiolitis, obliterative bronchiolitis, bronchiolectasia and bronchiectasis. Morphometric changes in the HNO3-treated hamsters included decreased lung volumes and decreased internal surface areas. Biochemical changes showed increases in lung weight and in total collagen and elastin. The model is useful because a prolonged insult to the airways develops rapidly and persists over a long period of time, important features for investigations designed to study the effects of superimposed insults upon pre-existent airway lesions.

Topics: Animals; Bronchi; Bronchiectasis; Bronchitis; Cricetinae; DNA; Elastin; Female; Lung; Lung Diseases; Male; Mesocricetus; Nitrates; Nitric Acid; Pulmonary Alveoli

Altogether 274 patients with different pulmonary diseases were examined for the activity of trypsin and elastase of the blood and the level of their inhibitors. The concentration of antibodies to collagen and elastin was also measured. In acute chronic pneumonia or exacerbation, the activity of the enzymes increased, the concentration of antibodies to collagen and elastin rose. In acute pneumonia, the titer of antibodies to collagen and elastin persisted for 1-1.5 months, in CNPD and tuberculosis for 4-8 months.

Topics: Antibodies; Collagen; Connective Tissue; Elastin; Humans; Lung Diseases; Pancreatic Elastase; Peptide Hydrolases; Trypsin; Trypsin Inhibitors

Groups of Fischer-344 rats were exposed to either filtered air, 0.4, 1.4, or 4.0 ppm acrolein for 62 days (6 h/day, 5 days/week). Mortality was observed only in the 4.0 ppm chamber, where 32 of 57 male rats died, but none of the 8 exposed females died. The lungs of the 4.0 ppm group were heavier than those of the larger control animals. Relative to controls, there was a 20% increase in total dry lung weight while the percent dry weight decreased 1.5% in the high dose group. This increased dry weight and the absence of significant changes in the DNA and protein content per unit dry weight indicated that the greater lung weight observed in this group was in part due to increased cellularity. Lung connective tissue content was increased as a result of subchronic acrolein exposure. The amount of elastin per unit dry weight was 173% of control values in the animals exposed to 4.0 ppm acrolein. Collagen levels were elevated in both the 1.4 and 4.0 ppm groups, 113 and 137%, respectively, of control values. Histologically, the 4.0 ppm animals demonstrated bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema. Exposure related lesions were observed in only 3 of the 31 rats examined from the 1.4 ppm chamber and in none of the animals exposed to 0.4 ppm acrolein.

Topics: Acrolein; Aldehydes; Animals; Body Weight; Collagen; DNA; Edema; Elastin; Female; Kinetics; Lung; Lung Diseases; Male; Necrosis; Organ Size; Proteins; Rats; Rats, Inbred F344

72 cases of diffuse interstitial lung diseases were observed from 1969 to 1976. Specimens removed from 47 patients were subjected to the whole spectrum of reactions. According to variation of both elastin and collagen, the following groups were outlined: group A: mycobacteriosis, farmer's lung, sarcoidosis and silicosis; group B: chronic eosinophilic pneumonia, lymphocytic interstitial pneumonia, post-tuberculous pulmonary fibrosis, and group C: X-ray pneumopathy, desquamative interstitial pneumonia, sclerodermic pneumopathy and chronic pulmonary fibrosis (primary chronic fibroadenomyosis). Each of these groups presents a close relationship between histochemical, radiological, clinical and functional findings.

Topics: Collagen; Elastin; Glycosaminoglycans; Heparin; Humans; Lung; Lung Diseases; Phosphatidylcholines; Pulmonary Fibrosis

Lung calcification was detected in four out of 29 long-term dialysed patients on whom postmortem examinations were performed between 1967 and 1980. On light microscopy, calcification showed either a finely granular and linear localization along the alveolar septa, or a coarse and widespread parenchymal distribution. Histochemical studies revealed evidence of calcium, magnesium and phosphate ions in the deposits. Ultrastructural examination of the less severely involved alveolar septa showed selective deposition of calcium salts within an increased amount of elastin. The deposits consisted of electron dense roundish granules with a concentric laminar structure. They appeared either single or conglomerated in polycyclic formations, supposedly representing the progressive steps of the mineralization process, at first localized within elastin and progressively spreading outside it. The high magnesium content of the deposits suggests that the serum concentration of this ion may play an important role in visceral calcification of long-term dialysed patients.

Topics: Adult; Calcinosis; Calcium; Elastin; Female; Humans; Kidney Failure, Chronic; Lung; Lung Diseases; Magnesium; Male; Middle Aged; Renal Dialysis

Vineyard sprayer's lung is an occupational lung disease, caused by inhalation of Bordeaux mixture (1-2% aqueous solution of copper sulfate, neutralized with hydrated lime). Experimental studies in mice after a longstanding exposition to copper sulfate aerosol showed focal accumulations of macrophages in alveoli with different cytoplasmatic inclusions, focal interstitial granuloma formation, increased formation of collagenous and elastic fibers, and increased production of surfactant phospholipids, phagocytosed by macrophages. As a conclusion of these results, copper seems to be the responsible agent for the development of lung changes, seen in vineyard sprayer's lung.

Topics: Aerosols; Animals; Collagen; Copper; Copper Sulfate; Elastin; Inclusion Bodies; Lung Diseases; Macrophages; Mice; Mice, Inbred Strains; Microscopy, Electron; Occupational Diseases; Pulmonary Alveoli; Pulmonary Surfactants

Topics: Animals; Cell Wall; Collagen; Connective Tissue; DNA; Elastin; Female; Granuloma; Lung Diseases; Mycobacterium bovis; Rats; Rats, Inbred F344

Topics: Animals; Collagen; Disease Models, Animal; Elastin; Hemorrhage; Inflammation; Intubation, Intratracheal; Lung; Lung Diseases; Papain; Pulmonary Edema; Pulmonary Emphysema; Rabbits

Topics: Desmosine; Elastic Tissue; Elasticity; Elastin; Humans; Isodesmosine; Lung Diseases; Models, Biological; Models, Molecular; Proline; Vascular Diseases

Topics: Air Pollution; Animals; Autoradiography; Collagen; Elastin; Female; Hyperplasia; Lung; Lung Diseases; Male; Mice; Microscopy, Electron; Organ Size; Oxygen Consumption; Pulmonary Alveoli; Smog