Effects of Neutrophil Elastase

A bstract. The effects of neutrophil elastase on endothelial prostacyclin (PGI2) production, nucleotide release, and responsiveness to vasoactive agents were compared with the effects of cathepsin G (the other major neutral protease of neutrophils), pancreatic elastase, trypsin, chymotrypsin, and thrombin. PGI2 production by pig aortic endothelial cells cultured on microcarrier beads and perfused in columns was stimulated in a dose-dependent manner by trypsin, chymotrypsin, and cathepsin G (1-100 ,ug/ml for 3 min). Thrombin, while active at low concentrations (0.1-10 National Institutes of Health U/ml), induced smaller responses. Neutrophil and pancreatic elastase had little or no effect on PG12 production. Dose-dependent, selective release ofadenine nucleotides was induced by neutrophil elastase (3-30 .g/ml). The other proteases were much less active; for example, trypsin (100 tg/ml) induced a response only -5% as great as did 30 ,ug/ml neutrophil elastase. After exposure to 30 ug/ml neutrophil elastase, cells did not exhibit the characteristic burst of PG12 production in response to extracellular ATP; responsiveness gradually returned after 40-120 min. This effect was not seen with the other proteases. Elastase partly inhibited re-