elastin and Bronchitis

Alpha 1 antiprotease is the major antiprotease (or antielastase) in the lungs. Neutrophils are the major source of elastase. Elastases damage interstitial elastic fibers giving rise to elastase-antielastase imbalance and to emphysema. Lung volume and volume-pressure (VP) curve is shifted up and to the left in elastase treated hamsters compared to the controls; quasi-static compliance increases from 0.52 ml/cm to 0.92 ml/cm in the elastase treated animals. The histologic, stereologic and physiologic data of hamster's emphysema are all similar to the changes observed in human emphysema. Cigarette smoke is rich in oxidants inactivating alpha 1 antiproteases. There is also a decrease in the level of alpha 1 antiproteases in lavage fluid of smokers. An intensive search is now underway for synthetic antielastases which might be safely given to persons who are at risk of developing emphysema.

Topics: alpha 1-Antitrypsin; Amino Acid Chloromethyl Ketones; Animals; Bronchitis; Cricetinae; Danazol; Dogs; Elastin; Humans; Lung; Macrophages; Neutrophils; Pancreatic Elastase; Pulmonary Alveoli; Pulmonary Emphysema; Rats; Smoking

Cigarette smoke (CS)-induced macrophage activation and airway epithelial injury are both critical for the development of chronic obstructive pulmonary disease (COPD), while the eventual functions of autophagy in these processes remain controversial. We have recently developed a novel COPD mouse model which is based on the autoimmune response sensitized by CS and facilitated by elastin. In the current study, we therefore utilized this model to investigate the roles of autophagy in different stages of the development of bronchitis-like airway inflammation. Autophagic markers were increased in airway epithelium and lung tissues, and

Topics: Animals; Autophagy; Biomarkers; Bronchitis; Cell Line; Cells, Cultured; Disease Models, Animal; Disease Susceptibility; Elastin; Gene Expression; Humans; Immunohistochemistry; Lung; Macrophages, Alveolar; Male; Matrix Metalloproteinase 12; Mice; Tobacco Smoke Pollution

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs. During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes. The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study.. The COPDGene study recruited 10,300 COPD patients in 21 centers. A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE). Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed.. The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05). EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%. C1M was inversely associated with forced expiratory volume in 1 s (FEV. These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema. Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials.

Topics: Aged; Biomarkers; Bronchitis; Collagen Type I; Collagen Type VI; Colorado; Comorbidity; Elastin; Extracellular Matrix Proteins; Female; Humans; Lung; Male; Middle Aged; Prevalence; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Pulmonary Eosinophilia; Reproducibility of Results; Risk Factors; Sensitivity and Specificity

Elastic fibers required to maintain bronchial patency during ventilation may be damaged in asthma as a result of repair following inflammation or stretching during exacerbations. Fifteen normal subjects and 40 asthmatics of variable severity were studied. Bronchial biopsies were obtained from a subsegmental bronchus using a flexible bronchoscope. The elastic fibers were examined using orceine-eosine sustaining and/or immunohistochemistry with two monoclonal antibodies against elastin or transmission electron microscopy (six asthmatics and four control subjects). Orceine-eosine staining revealed that most normal subjects had normal fibers throughout the submucosa whereas of the 21 asthmatics analyzed only three had a normal superficial elastin network. In five patients, elastin had virtually disappeared. In the remaining patients, fibers appeared fragmented. The deeper layer of elastic fibers was abnormal in 17 asthmatics, fibers being patchy, tangled, and thickened. The fragmentation of the superficial network of elastic fibers shown in asthmatics was confirmed by immunohistochemistry. Electron microscopy studies suggested that the elastinolytic process and fragmentation of elastic fibers occurred in asthmatics. Elastinolysis occurs in the airways of asthmatics possibly as a result of repair elicited by chronic inflammation. Mechanical stretch induced by breathing and edema may lead to the fragmentation of fibers in asthmatic airways.

Topics: Adult; Antibodies, Monoclonal; Asthma; Biopsy; Bronchi; Bronchitis; Bronchoscopes; Case-Control Studies; Coloring Agents; Edema; Elastic Tissue; Elastin; Eosine Yellowish-(YS); Fluorescent Dyes; Humans; Immunohistochemistry; Microscopy, Electron; Middle Aged; Oxazines; Respiratory Mechanics

The aim of the study was to examine the effects of bronchitis on elastin-derived peptides (EP) and antielastin antibodies (AEAb) in serum. Using an ELISA technique, these parameters were assessed in children aged 6 months to 15 years: 36 had recurrent bronchitis (RB), 34 had obstructive bronchitis (OB) and 37 were healthy children (C). A comparison of the levels of the investigated compounds in the acute phase (I) and stage without signs of diseases (II) was studied. The EP data show non-significant changes in the RB and OB groups in comparison with group C. Children with OB had significantly lower levels of AEAb in IgA, IgG and IgM class antibodies, while those with RB in the IgG class in comparison with group C in both examinations. In examination 1, AEAb in IgA and IgM classes were significantly lower in children with OB than with RB.

Topics: Adolescent; Antibodies; Bronchitis; Child; Elastin; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Peptides; Recurrence

In recent years a rising interest has developed among the authors studying the problems of pathogenesis and treatment of chronic bronchitis and pulmonary emphysema in the factors responsible for the immune equilibrium of the respiratory system. In particular, the correlation has been stressed between the levels of inflammation mediators and the activity of proteolytic enzymes and their inhibitors in lung tissue. Most studies seem to confirm the validity of the elastase-antielastase concept. Among the environmental factors directly responsible for the development of these diseases tobacco smoke and other irritant fumes (SO2NO2) are mentioned. This concept had been the foundation for trials of therapeutic use of inhibitors of elastolytic enzymes.

Topics: Adult; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Bronchitis; Elastin; Humans; Lung; Middle Aged; Oxygen Inhalation Therapy; Pancreatic Elastase; Pulmonary Emphysema; Smoking

We have determined the effect of two elastase-specific synthetic low molecular weight substrates, L-pyroglutamylprolylvaline-paranitroanilide and succinyltrialanyl-paranitroanilide, together with insoluble elastin-fluorescein, on the determination of the neutrophil elastase (NE) inhibitory capacity of purified alpha 1-proteinase inhibitor (alpha 1-PI) and bronchial antileukoprotease (ALP). In addition, the inhibitory capacities of mixtures of alpha 1-proteinase inhibitor, antileukoprotease and alpha 2-macroglobulin prepared in ratios similar to that in lung secretions were determined. Purified inhibitors, alone or in combinations, inhibited about 1 mole neutrophil elastase per mole inhibitor when assessed using synthetic substrates. However, when elastin-fluorescein was used in the assay system, the purified inhibitors showed an inhibitory capacity that was 40-85% of the value obtained using synthetic substrates. Even less inhibition was observed when mixtures of inhibitors were assessed using elastin-fluorescein (23-44% of the value for synthetic substrates). Our data indicate that results of elastase inhibitor activity measurements depend on the type of substrate which has been used.

Topics: alpha 1-Antitrypsin; alpha-Macroglobulins; Blood Proteins; Bronchi; Bronchitis; Chronic Disease; Elastin; Humans; Molecular Weight; Neutrophils; Oligopeptides; Pancreatic Elastase; Protease Inhibitors; Proteinase Inhibitory Proteins, Secretory; Proteins; Pyrrolidonecarboxylic Acid

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

Topics: Bronchitis; Elastin; Humans; Methods; Pancreatic Elastase; Sputum

Topics: Adult; Aged; Bronchitis; Collagen; Elastin; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Middle Aged; Pulmonary Emphysema