elastin and Lung-Diseases--Obstructive

Once considered as inert, the extracellular matrix recently revealed to be biologically active. Elastin is one of the most important components of the extracellular matrix. Many vital organs including arteries, lungs and skin contain high amounts of elastin to assure their correct function. Physiologically, the organism contains a determined quantity of elastin from the early development which may remain physiologically constant due to its very long half-life and very low turnover. Taking into consideration the continuously ongoing challenges during life, there is a physiological degradation of elastin into elastin-derived peptides which is accentuated in several disease states such as obstructive pulmonary diseases, atherosclerosis and aortic aneurysm. These elastin-derived peptides have been shown to have various biological effects mediated through their interaction with their cognate receptor called elastin receptor complex eliciting several signal transduction pathways. In this review, we will describe the production and the biological effects of elastin-derived peptides in physiology and pathology.

Topics: Aortic Aneurysm; Atherosclerosis; Elastin; Extracellular Matrix; Humans; Lung Diseases, Obstructive; Peptide Fragments; Receptors, Cell Surface; Signal Transduction

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

The elastic properties of many tissues such as the lung, dermis, and large blood vessels are due to the presence of elastic fibers in the extracellular space. These fibers have been shown by biochemical and ultrastructural analysis to be comprised of two distinct components, a more abundant amorphous component and the microfibrillar component. The microfibrillar component is found in 10- to 12-nm fibrils which are located primarily around the periphery of the amorphous component but, to some extent, interspersed within it. The protein, elastin, makes up the highly insoluble amorphous component and is responsible for the elastic properties. Elastin is found throughout the vertebrate kingdom except for very primitive fish and possesses an unusual chemical composition consonant with its characteristic physical properties. Elastin is composed largely of glycine, proline, and other hydrophobic residues and contains multiple lysine-derived cross-links, such as the desmosines, which link the individual polypeptide chains into a rubber-like network. The intervening, hydrophobic regions of the polypeptide chains between the cross-links are highly mobile, and the elastic properties of the fibers can be described in terms of the theory of rubber elasticity. Recent application of recombinant DNA techniques has led to further understanding of the structure of elastin. Analyses of the bovine and human elastin genes have demonstrated that the hydrophobic and cross-linking domains are encoded in separate exons. These exons tend to be small, varying from 27 to 114 base pairs, and are separated by large intervening sequences. Furthermore, DNA sequence analysis has demonstrated that the elastin molecule contains two cysteine residues which were not previously identified near the carboxy terminus and which may be important in the interaction of elastin with other extracellular matrix proteins. Further DNA sequencing should determine the complete amino acid sequence of elastin. Biosynthetic studies and in vitro translation of elastin mRNA have demonstrated that a 72,000-dalton polypeptide, designated tropoelastin, is the initial translation product. Analysis of several developing systems has demonstrated that elastin synthesis is controlled by the level of elastin mRNA. After packaging into membrane-bound vesicles in the Golgi apparatus, tropoelastin is secreted by exocytosis into the extracellular space where it is cross-linked by a copper-requiring extracellular enzyme, lys

Topics: Amino Acid Sequence; Amino Acids; Animals; Aorta; Base Sequence; Biological Evolution; Bone Diseases; Chemical Phenomena; Chemistry; Cutis Laxa; DNA; Elastin; Genes; Genetic Diseases, Inborn; Humans; Lung Diseases, Obstructive; Macromolecular Substances; Marfan Syndrome; Microscopy, Electron; Protein-Lysine 6-Oxidase; Pseudoxanthoma Elasticum; RNA, Messenger; Species Specificity; Syndrome; Tropoelastin; Vascular Diseases

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.

Topics: Aged; Desmosine; Double-Blind Method; Drug Administration Schedule; Elastin; Female; Humans; Leukocyte Elastase; Lung Diseases, Obstructive; Male; Protease Inhibitors; Thiophenes; Time Factors

Early diagnosis and monitoring progression of chronic diseases in elastin-rich tissues, such as chronic progressive lymphoedema in draught horses and chronic obstructive pulmonary disease (COPD) is still a real challenge in the horse. Use of an enzyme-linked immunosorbent assay (ELISA) to detect anti-elastin antibody (AEAb) levels might be useful to assess the status of such diseases. Baseline levels, representing physiological breakdown of elastin in normal horses, are not available at present.. Levels of AEAb in healthy horses are generally low and follow the same age-related pattern as found in man. Therefore, elevation of AEAb levels in serum can be used to evaluate pathological elastin breakdown in elastin-rich tissues.. Sera of 84 clinically healthy Warmblood horses were evaluated for the presence of AEAbs by means of a modified version of an ELISA technique used in man. The horses were divided in 5 age groups: A) < 4 months; B) 4-23 months; C) 2-3 years; D) 4-10 years; and E) > 11 years.. Antibodies to elastin were found in all equine serum samples tested. Their levels were lowest in Group A, low in Groups B and E and highest in animals age 2-10 years.. Measuring AEAbs in serum of horses by an ELISA technique proved to be possible and levels were stable during well-defined life stages.. Changes in AEAb levels are expected to be useful for early diagnosis and for monitoring progression of diseases that affect elastin-rich tissues, such as chronic progressive lymphoedema and COPD.

Topics: Aging; Animals; Autoantibodies; Chronic Disease; Diagnosis, Differential; Disease Progression; Elastin; Enzyme-Linked Immunosorbent Assay; Horse Diseases; Horses; Lung Diseases, Obstructive; Lymphedema; Peptides; Reference Values; Sensitivity and Specificity; Severity of Illness Index

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p< or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin Deficiency; Bronchiectasis; Cross-Linking Reagents; Cross-Sectional Studies; Cystic Fibrosis; Desmosine; Elastin; Electrophoresis, Capillary; Emphysema; Extracellular Matrix; Female; Humans; Isodesmosine; Longitudinal Studies; Lung Diseases, Obstructive; Male; Middle Aged

To determine whether samples of tracheal epithelial lining fluid (TELF) obtained from horses have elastinolytic activity characteristic of metalloproteinases, to compare elastinolytic activity in TELF obtained from healthy horses and horses with chronic obstructive pulmonary disease (COPD), and to determine whether chemically modified tetracycline-3 (CMT-3) inhibits elastinolytic activity in TELF ANIMALS: 10 horses with COPD and 10 healthy control horses.. Zymography and fluorometry were used to measure elastinolytic activity, and EDTA was used to inhibit elastinolytic activity and verify that the activity was attributable to metalloproteinases. Possible inhibition of elastinolytic activity with CMT-3 was studied in vitro.. Elastinolytic activity was found in TELF obtained from all horses, and this activity was significantly higher in TELF obtained from horses with COPD than in TELF obtained from healthy horses. For all samples, EDTA and CMT-3 inhibited elastinolytic activity.. Elastinolytic activity is detectable in TELF obtained from horses and seems to be attributable to metalloproteinases. Elastinolytic activity in TELF is significantly inhibited by CMT-3. Elastinolytic activity in TELF can be detected by means of zymography or fluorometry. Increased elastinolytic activity may reflect destruction of pulmonary tissue in horses with COPD. Chemically modified tetracyclines such as CMT-3 may provide an additional treatment possibility for horses with COPD.

Topics: Animals; Down-Regulation; Edetic Acid; Elastin; Female; Fluorometry; Horse Diseases; Horses; Lung Diseases, Obstructive; Male; Molecular Weight; Protease Inhibitors; Respiratory System; Tetracyclines

The relationship between abdominal aortic aneurysms (AAA) and chronical obstructive pulmonary disease (COPD), and in particular the suggested common elastin degradation caused by elastase and smoking was analysed by a cross sectional population mass screening study for AAA, and a prospective cohort study of small AAA. All previous computer-hospital-recorded diagnoses were received concerning 4,404 men invited to screening for AAA. One hundred and forty-one had AAA (4.2%). They were asked for an interview, a clinical examination, and a blood sample. Men with an AAA of 3-5 cm were offered annual control-scans to check for expansion. Of COPD-patients, 7.7% had AAA (crude OR = 2.05), however the adjusted OR was only 1.53 after adjusting for other co-existing diseases (p = 0.13). The mean annual expansion was 2.74 mm per year in COPD patients and 2.72 in non-COPD patients, and 4.7 mm in oral steroid-users compared to 2.6 in non-steroid-users (p < 0.05). S-elastin-peptides (SEP) and P-elastase-alpha1-antitrypsin-complexes (PEAC) were negatively correlated to FEV1 in COPD-patients. However, SEP, beta-agonist-treatment, and FEV1 was positively correlated to expansion by multivariate regression analysis, while PEAC and S-alpha1-antitrypsin did not influence expansion, suggesting elastase plays a major role in the pathogenesis of COPD but not in AAA. The high prevalence of AAA among patients with COPD is more likely to be caused by medication and coexisting diseases rather than a common pathway of pathogenesis.

Topics: alpha 1-Antitrypsin; Aortic Aneurysm, Abdominal; Cohort Studies; Cross-Sectional Studies; Denmark; Elastin; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Smoking; Vital Capacity

It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amino Acids; Biomarkers; Collagen; Desmosine; Elastin; Female; Humans; Isodesmosine; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Smoking

The effects of ozone (O3) and nitrogen dioxide (NO2) on the solubility and proteolytic susceptibility of elastin were examined to better understand how these oxidant air pollutants might damage the lung. In vitro O3 exposures at pH 7.4 resulted in the complete solubilization of elastin, but NO2 had no effect on solubility. The initial solubilization rate was 65 micrograms/mumol of O3, which increased to 150 micrograms/mumol in the midregion of a sigmoidal solubilization curve. Peptide fragments of the O3-solubilized elastin ranged in size from 5 to 20 kD. The conversion of insoluble elastin into soluble fragments by O3 was not due to the destruction of desmosine crosslinks. The effect of O3 on the proteolytic susceptibility of elastin was measured using insoluble elastin recovered from exposures that resulted in 5.3%, 12.8%, and 26.3% solubilization. Human neutrophil elastase (HNE) digested the remaining insoluble elastin samples 4.3, 6.0, and 9.8 times faster than unexposed elastin. In contrast, NO2-exposed elastin was no more susceptible to digestion by HNE. Ascorbate, EDTA, and uric acid reduced the proteolytic susceptibility of O3-exposed elastin, but mannitol afforded no protection. These findings indicate that the inhalation of O3 may contribute to lung disease by directly damaging elastin and by increasing its susceptibility to proteolysis, whereas NO2 probably damages lungs via alternative mechanisms.

Topics: Air Pollutants; Animals; Antioxidants; Cattle; Elastin; Humans; In Vitro Techniques; Leukocyte Elastase; Lung Diseases, Obstructive; Neutrophils; Nitrogen Dioxide; Ozone; Pancreatic Elastase; Peptide Fragments; Solubility

Topics: Animals; Cystic Fibrosis; Elastin; Endothelium, Vascular; Humans; Hypertension, Pulmonary; Hypoxia; Lung Diseases, Obstructive; Muscle, Smooth, Vascular; Pancreatic Elastase

Topics: Adult; Elastin; Humans; Lung Diseases, Obstructive; Middle Aged

Proteolysis of elastic fibers is central to the development of emphysema, and a simple, noninvasive assay of elastin degradation would be useful in diagnosis and in therapeutic monitoring. We have adapted an indirect enzyme-linked immunosorbent assay (ELISA) to determine plasma, urine, and bronchoalveolar lavage fluid (BALF) elastin peptide concentrations in nonsmokers, healthy smokers, and patients with chronic obstructive pulmonary disease (COPD). Plasma elastin peptide concentrations were significantly higher in subjects with COPD (66.8 +/- 5.8 ng/ml, n = 10) compared with nonsmokers (23.4 +/- 4.6 ng/ml, n = 12), and healthy smokers had intermediate values (36.0 +/- 6.8, n = 6), p less than 0.05. Urine values (both unadjusted and normalized to urine creatinine concentration) were approximately 10-fold higher than plasma in all subject groups, and the relative differences among groups were the same as for plasma with values of 910.8 +/- 105.6, 358.1 +/- 101.2, and 281.0 +/- 67.8 ng/ml for subjects with COPD (n = 10), healthy smokers (n = 6), and healthy nonsmokers (n = 12), respectively. Poor recovery of BALF in COPD subjects reduced differences in the BALF elastin peptide concentrations among subjects groups, although the healthy smokers and COPD subjects tended to have higher amounts. Assuming some dilution due to lavage technique, elastin peptide concentrations were estimated to be substantially higher in epithelial lining fluid than in plasma, suggesting lung as a significant source of elastin peptides in COPD. This is the first application of elastin peptide measurement to human urine or BALF, and we conclude that this assay in urine is useful in characterizing elastin turnover in patients with or at risk for emphysema.

Topics: Adult; Bronchoalveolar Lavage Fluid; Elastin; Enzyme-Linked Immunosorbent Assay; Humans; Lung; Lung Diseases, Obstructive; Middle Aged; Reproducibility of Results; Smoking

One prediction of the protease-antiprotease hypothesis of chronic obstructive pulmonary disease (COPD) pathogenesis is the appearance of elastin-derived degradation products in the plasmas of affected patients that are due to the breakdown of alveolar interstitial elastin by an excess of elastolytic activity in the lung. We previously demonstrated a significant elevation of plasma elastin-derived peptides (EDP) in subjects with COPD in comparison with asymptomatic smokers with normal spirometry or normal nonsmokers. To better determine the selectivity of the assay for EDP as a marker of COPD, we measured plasma EDP levels in different patient populations. These included subjects with COPD, subjects with diseases that may involve accelerated elastolysis (pneumonia, atherosclerotic vascular disease, and inflammatory arthritis), subjects with diseases hypothesized to involve pulmonary inflammation without elastolysis (asthma and acute tracheobronchitis), asymptomatic smokers with normal spirometry, and healthy, nonsmoking subjects. Mean plasma EDP levels in subjects with COPD were elevated above those in all other subjects (p less than 0.01). The prospective analyses of specificity and sensitivity of plasma EDP levels as markers of COPD gave values of 91 and 65%, respectively. Utilizing receiver operating characteristic curve analysis to assess the diagnostic and screening performance of plasma EDP as a test for COPD (perfect test equals an area under the curve of 1.0), the area under the curve was 0.87, which compares favorably with many widely used clinical tests. These data demonstrate that the assay for plasma EDP is a quantitative, easily measured, and highly specific marker for subjects with COPD.

Topics: Adult; Aged; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Risk Factors; ROC Curve; Sensitivity and Specificity; Smoking

The protease-antiprotease hypothesis of emphysema development suggests that degradation of elastin in the lung interstitium may give rise to abnormal quantities of circulating elastin-derived peptides (EDP) during periods of inflammation. Recent studies have shown a relationship between emphysema and high levels of EDP in human plasma. This report characterizes elastin digests on the basis of antigenicity, size, and method of preparation, as well as the size distribution of EDP found in the plasmas of nonsmokers, smokers, and emphysema patients. Gel filtration of elastin digests prepared by hydrolysis of human lung elastin using a low (1:500) ratio of neutrophil elastase to elastin generated a broad protein peak of approximately 70,000 daltons. In contrast, a high (1:25) ratio of neutrophil elastase to human lung elastin gave a broad protein peak, with a size distribution in the 10,000 to 30,000 dalton range. This digest showed distinct immunochemical properties. A polyclonal antibody directed against the low-ratio digest showed a minimum detection of 2 ng/ml for the homologous antigen but required 1,000 ng/ml of the high-ratio digest for detectable inhibition in an indirect ELISA assay. Gel filtration of plasmas from normal nonsmokers and the majority of normal smokers revealed a single immunoreactive EDP fraction of approximately 70,000 daltons. Plasmas from selected normal smokers and emphysema patients with high levels of circulating EDP (greater than 90 ng/ml) fractionated into a complex pattern of peptides in which the 70,000 dalton component represented 50% of the immunoreactive material and several lower molecular weight peptides represented the remaining circulating elastin antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antigens; Chemical Fractionation; Elastin; Enzyme-Linked Immunosorbent Assay; Forced Expiratory Volume; Humans; Lung; Lung Diseases, Obstructive; Peptides; Reference Values; Respiratory Function Tests; Smoking

Several congeners of elasnin (I) have been synthesized and shown to inhibit human leukocyte elastase (HLE). The C-3 alkyl substituted 2-pyrones 11 and 12 were found to be the most effective inhibitors of the enzyme. These compounds are highly specific in their inhibitory activity.

Topics: Elastin; Humans; In Vitro Techniques; Leukocytes; Lung Diseases, Obstructive; Pancreatic Elastase; Pyridones; Structure-Activity Relationship

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and significant impairment of lung function usually occurs before the disease is diagnosed. Because lung elastin degradation appears to be a prerequisite for the development of the disease, immunologic detection of elastin-derived peptides in the blood might be an effective approach to the early detection and monitoring of the disease. We here report an improved enzyme-linked immunosorbent assay for elastin peptides using a peroxidase-antiperoxidase complex as the reporter group. The assay is sensitive to 2 ng/ml elastin peptides. We show that for optimal, reproducible results the assay should be carried out at 16 degrees C rather than at room temperature and that determinations should be made on plasma containing protease inhibitors rather than on serum. The levels of elastin-derived peptides appeared to remain relatively constant when multiple samples were taken during a 5- to 10-wk period from individual subjects. In addition, patients with COPD had elevated elastin peptide levels (127 +/- 47 ng/ml) compared with levels in normal nonsmokers (58 +/- 17 ng/ml), whereas normal smokers had values intermediate between the 2 groups (mean peptide levels of 76 +/- 42 ng/ml). A small group of normal smokers (20%) had elevated elastin peptide levels similar to those in the emphysema group and may represent that group of smokers who are at risk of developing obstructive lung disease.

Topics: Animals; Elastin; Enzyme-Linked Immunosorbent Assay; Goats; Humans; Immune Sera; Immunoenzyme Techniques; Lung Diseases, Obstructive; Peptides; Rabbits; Temperature

Human serum was found to contain enzyme activities hydrolyzing succinyl trialanine paranitroanilide and 3H-kappa-elastin Sepharose substrates. Both types of activities could be partly abolished by serine active site titrants (phenylmethanesulfonylfluoride, diisopropylphosphorofluoridate) and partly by neutral chelating agents (EDTA; 1-10-phenanthroline). The combination of phenylmethanesulfonylfluoride and EDTA gave a complete inhibition of human serum elastase-type activities indicating the presence of at least two different types of elastases (serine and metalloproteases) in human serum. In nonsmokers, the average serum elastase-type activity on succinyl trialanine paranitroanilide was found equal to 78.1 ng/ml porcine pancreatic elastase equivalents and on 3H-kappa-elastin sepharose beads equal to 688.8 ng/ml. No statistically significant differences were observed in elastase levels in the sera of individuals presenting clinical symptoms of atherosclerosis. The sera of patients suffering from chronic obstructive lung diseases contained, however, higher amounts of elastase-type activities, respectively equal to 237.2 ng/ml on succinyl trialanine paranitroanilide and 1,096 ng/ml on 3H-kappa-elastin Sepharose beads and was quantitatively significant when compared with control subjects.

Topics: Adult; Aged; Arteriosclerosis; Elastin; Humans; Lung Diseases, Obstructive; Middle Aged; Oligopeptides; Pancreatic Elastase; Sepharose; Substrate Specificity

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and usually significant impairment of lung function has occurred before the disease is diagnosed. It is likely that destruction of the elastic fiber is a prerequisite for the development of the disease, and it is possible that immunologic identification in the serum of peptides derived from lung elastin degradation might be an effective approach to the early detection and monitoring of the disease. We prepared antibodies to peptides derived from human lung parenchymal elastin and used these antibodies in an enzyme-linked immunosorbant assay to quantitate elastin-derived peptides in the serum of 39 normal control nonsmokers, 33 smokers with normal lung function, and 40 patients with COPD. On average, statistically significant higher levels of elastin-derived peptides were found in the normal smokers and COPD patients compared to the controls. Further work with larger numbers of subjects is necessary to determine whether such a test is effective in identifying those individuals who are at risk of developing COPD.

Topics: Antibodies; Elastin; Enzyme-Linked Immunosorbent Assay; Humans; Lung Diseases, Obstructive; Peptides; Pulmonary Emphysema; Serologic Tests

Desmosine is a cross-link amino acid unique to elastin. Previous work has shown that during turnover in the body, desmosine is not reused, and that desmosine is not absorbed from the intestine. Instead, all desmosine released in the course of elastin metabolism is excreted in the urine attached to low molecular weight peptides. Therefore, measurement of desmosine in acid-hydrolysates of urine might be used to monitor elastin breakdown in several pathologic states, including pulmonary emphysema. In the present report, we have described a sensitive, highly specific radioimmunoassay capable of detecting as little as 200 pg of desmosine in acid-hydrolysates of urine. The assay was specific for desmosine; cross-reactivity with merodesmosine, isodesmosine, lysine, and mixed amino acids was 0.25%, 0.1%, less than 0.0003%, and 0%, respectively. Twenty-three normal, nonsmoking subjects had a mean 24-hr desmosine excretion of 47 +/- 15 microgram. In a group of smokers with evidence of chronic obstructive disease and/or lung infection, the values for desmosine excretion ranged from 40 to 400 microgram/24 h. Desmosine radioimmunoassay may find application in the study of diseases involving increased destruction of elastin in the body.

Topics: Adolescent; Adult; Aged; Amino Acids; Desmosine; Elastin; Humans; Lung Diseases, Obstructive; Middle Aged; Radioimmunoassay; Smoking