Role Of Elastase Research Articles

Bacterial Lipopolysaccharide Enhances Chemoattractant-Induced Elastase Secretion by Human Neutrophils

Bacterial lipopolysaccharide (LPS) has previously been shown to enhance a number of chemoattractant-induced responses by human neutrophils. The possible role of elastase, a neutral protease with broad substrate specificity, in neutrophil-mediated vascular injury of a variety of diseases prompted us to examine a) whether or not LPS enhances the direct chemoattractant-induced secretion of elastase, b) the quantitative requirements of LPS and chemotactic factors, and c) some structural requirements of LPS for this effect. Our results show that LPS at 10 ng/ml and above, enhanced formyl-methionyl-leucyl-phenylalanine-induced neutrophil secretion of elastase, as well as secretion of myeloperoxidase and vitamin B12-binding protein. This effect was independent of cytochalasins or surface stimulation, and thus may occur during chemotactic factor stimulation in vivo. LPS also enhanced neutrophil secretory responses to the complement fragments C5a, C5a des arg, and, to a lesser degree, to leukotriene B4 and platelet-activating factor. This enhancement effect appeared to require the presence of the lipid A moiety and/or parts of the core polysaccharide but not the O-antigen portion of the LPS molecule. Our findings identify a possible LPS-dependent mechanism of neutrophil elastase-mediated tissue injury in Gram-negative infections.

Bacteriology of the cervix in cases of infertility: effect on human and animal spermatozoa and role of elastase.

Microorganisms such as Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans isolated from cervices of infertile human females inhibited motility and agglutinated human, cow bull, buffalo bull, and rat spermatozoa in vitro. Fifty percent of the infertile females studied carried elastase-positive microorganisms. Cell-free culture supernatants of 72-hr-old elastase-positive cultures were spermicidal within 60 min of contact with sperm, while elastase-negative cultures were spermicidal in 4-6 hr. Cultures of all the cervical isolates were spermicidal and agglutinated human, cow bull, buffalo bull, and rat spermatozoa, and these activities increased with age of the culture. Human sperm showed only tail-to-tail agglutination, while cow bull, buffalo bull, and rat spermatozoa showed mainly head-to-head agglutination. Spermicidal activity was also attributable to elastase, which was present more in 72-hr-old cultures than in 24-hr-old cultures.

Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis.

Many studies have been carried out in the past 10 yr dealing with the possible role of elastase in the pathogenesis of pulmonary emphysema. These include newer observations in animal models revealing augmentation of elastase-induced lesions by lathyrogens or by exposure to cigarette smoke. In general, the animal model experiments have focussed attention on repair-processes in the lung and shown that such processes may exert a major influence on the outcome of the initial proteolytic insult. Human studies exploring correlations between elastase levels in neutrophils or serum and development of disease have provided conflicting data; however, measurement of enzymes in pulmonary secretions have yielded more suggestive results. Assessments of lung elastase inhibitors in humans continue to support the importance of alpha-1-proteinase inhibitor in the protection of the lower respiratory tract, but newer information on locally produced, low molecular weight elastase inhibitors indicates that these, too, may play a significant role. Attempts have been made to link cigarette smoking to the development of emphysema at the chemical and cellular levels. These studies have focussed on: (1) the recruitment of elastase-producing leukocytes to smokers' lungs, (2) inactivation of lung elastase-inhibitors by tobacco products or by metabolites released from tobacco-stimulated lung cells, and (3) interference with elastin neosynthesis (repair) in the smoker. Additional information is also available concerning the biochemical properties of neutrophil and macrophage elastases, although it is still unclear which of these enzymes plays the predominant role in chronic lung injury associated with smoking. Perhaps the greatest advance in the emphysema field in recent years involves new discoveries concerning the structure and function of the alpha-1-proteinase (elastase) inhibitor. Applications of recombinant DNA technology and genetic engineering have made it possible to design modified inhibitors with striking new properties. These agents may enjoy significant clinical application in the not too distant future.

Alpha 2-plasmin inhibitor inactivation by human granulocyte elastase.

Plasminogen-binding human alpha 2-plasmin inhibitor is converted by human granulocyte elastase into its non-plasminogen-binding and finally into the inactive form of the inhibitor. This degradation of the plasmin inhibitor, described earlier as "spontaneously" occurring conversion, is shown in dodecyl sulfate polyacrylamide gel electrophoresis, in two-dimensional immunoelectrophoresis and by measuring the kinetics of plasmin inhibition. Experiments in the presence of normal human plasma required unphysiologically high concentrations of elastase to inactivate alpha 2-plasmin inhibitor, suggesting a role of elastase in this type of indirect fibrinolysis in a microenvironment only and not in systemic events.

Elastase activity: The role of elastase in aortic aneurysm formation

Elastase activity was studied in aortic tissue obtained from patients with aortic aneurysm and arteriosclerotic occlusive disease. Aneurysmal tissue demonstrates significantly greater activity than the arteriosclerotic aorta and the activity is localized to the intima and inner media. Aneurysms in patients without concomitant occlusive disease are larger than those in patients with occlusive disease and show greater elastase activity. Elastase activity of the aorta may determine aneurysm formation and may inhibit development of concomitant occlusive disease.

The role of elastase in the differentiation of Bacteroides nodosus infections in sheep and cattle

Eighty-seven Bacteroides nodosus isolates were examined for elastase production by clearing of elastin particles in TAS agar medium. These included 54 ovine virulent isolates, 28 ovine benign isolates and five bovine isolates. In addition 22 ovine virulent, 16 ovine benign and two bovine isolates were examined for decline in proteolytic activity over a 13-day period in the degrading proteinase test using hide power-azure as substrate. There was a remarkable correlation between elastase production, relative stability of proteolytic activity in the hide powder-azure test and virulence of B nodosus. Ovine virulent isolates invariably produced elastase whereas ovine benign isolates and bovine isolates were elastase negative. Bovine isolates produced only mild lesions in the feet of challenged sheep.

The role of elastases in the development of emphysema.

Enzymes which degrade elastin can disorganize the network of elastic fibers in the lungs of experimental animals and produce emphysema. Two sources of endogenous elastases in the lung are neutrophils and alveolar macrophages. The neutrophil elastase is an intracellular, granule-associated enzyme which is inhibited by α1-antitrypsin and has the capacity to produce emphysema in experimental animals. The recently identified macrophage elastase appears to be a secretory enzyme, not associated with granules and less effectively inhibited by α1-antitrypsin. The demonstration that macrophages from cigarette smokers release elastase in culture, and that cigarette smoke interferes with the action of inhibitors of elastase, suggests that elastases may be involved in the pathogenesis of emphysema in man. Further research is needed to establish whether degradation of elastin occurs in humans developing emphysema.

Mechanism of action of active elastase on pancreatic tissue

Acute pancreatitis developed 15 min after injection of 0.65 mg active elastase into the pancreatic duct. The histological changes in the gland tissue increased from the edematous form to necrotic pancreatitis with a hemorrhagic component, and with an increase in the dose of elastase injected up to 2.6 mg the elastic structures of the blood vessels were destroyed. The changes described above were accompanied by a decrease in the proelastase content in the pancreatic tissue and a decrease in the inhibitory power of the blood serum. The results are evidence of the important role of elastase in the pathogenesis of acute pancreatitis.

The Role of Elastase in the Digestion of E. coli Proteins by Human Polymorphonuclear Leukocytes I. Experiments in Vitro

The Role of Elastase in the Digestion of E. coli Proteins by Human Polymorphonuclear Leukocytes I. Experiments in Vitro