[Elastase inhibitors].
The serine proteinase elastase is located in the azurophil granules of mature circulating polymorphonuclear neutrophils. This neutrophil elastase or NE is a potent non specific serine protease which plays a role as bactericidal agent and in the degradation of immune complexes by intraphagosomal processes. It promotes inflammation when the granule contents are secreted in the extracellular environment. In certain pathological circumstances, an imbalance between NE and its major plasmatic inhibitor alpha 1-PI (formerly, alpha 1-antitrypsin) leads to abnormal tissue destruction and disease development. Genetic or acquired alpha 1-PI deficiency is thought to be involved in the pathogenesis of pulmonary emphysema. A variety of degenerative and degradative disorders are also associated to uncontrolled proteolysis by NE (rheumatoid arthritis, glomerulonephritis, adult respiratory distress symptom, psoriasis, cancer). Numerous inhibitors of NE have been reported. Various molecules are currently undergoing clinical trials for emphysema and other pulmonary diseases.
Reboud-Ravaux
M
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Laboratoire d'Enzymologie Moléculaire et Fonctionnelle, Département de Biologie Cellulaire Institut Jacques Monod, CNRS-Universités Paris VI et VII, 2 place Jussieu, 75251 Paris. reboud@ccr.jussieu.fr
D000818:Animals; D003374:Coumarins / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015195:Drug Design; D004549:Elastin / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D015394:Molecular Structure; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000502:physiology; D010588:Phagosomes / Q000201:enzymology; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000209:etiology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000515:alpha 1-Antitrypsin / Q000502:physiology; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000235:genetics
D003374:Coumarins; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D004549:Elastin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase