Human Neutrophils Release Serine Proteases Capable of Activating Prorenin
作者:
Victor Dzau,
Debra Gonzalez,
Carol Kaempfer,
Daniel Dubin,
Bruce Wintroub,
期刊:
Circulation Research
(OVID Available online 1987)
卷期:
Volume 60,
issue 4
页码: 595-601
ISSN:0009-7330
年代: 1987
出版商: OVID
关键词: protein activation;cathepsin G;elastase neukophil-angiotensin pathway;tissue renin angiotensin
数据来源: OVID
摘要:
Proteases from human neutrophils can generate angiotensin II directly from angiotensin I or angiotensinogen. We examined whether neutrophil protease also influences angiotensin formation by activating human prorenin (also called inactive renin). When incubated with partially purified plasma and amniotic prorenin, sonicates from 106 neutrophils resulted in 120 ± 30% and 1,240 ± 290% increase in renin activity, respectively. The pH optimum of neutrophil prorenin-activating enzyme(s) is 6.5-7.0, and the activity of the enzyme(s) is inhibited by a mixture of serine protease inhibitors but not by inhibitors of other proteases, suggesting that prorenin-activating enzyme(s) is a neutral serine protease(s). Stimulation of neutrophils by f-met-leu-phe in the presence of cytochalasin B resulted in release of prorenin-activating enzyme(s) in a dose-dependent fashion. We attempted to isolate prorenin-activating enzyme(s) from neutrophil granules using aprotinin-affinity and carboxymethyl cellulose chromatographies. Prorenin-activating enzyme(s) coeluted with cathepsin G and elastase activities. Prorenin activation was greatly inhibited by anticathepsin G antiserum. Purified cathepsin G activated prorenin in a dose-dependent fashion. Elastase probably also contributes to prorenin activation since purified elastase also activated human prorenin. We speculate that this neutrophilic angiotensin-generating system may play a role in the local generation and concentration of angiotensins by influencing multiple steps of the renin-angiotensin system.
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