Human neutrophils release serine proteases capable of activating prorenin.
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 10(6) 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.
Dzau
V J
VJ
Gonzalez
D
D
Kaempfer
C
C
Dubin
D
D
Wintroub
B U
BU
D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism / Q000502:physiology; D010450:Endopeptidases / Q000378:metabolism / Q000502:physiology*; D004792:Enzyme Precursors / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism / Q000502:physiology; D012083:Renin / Q000502:physiology*; D012697:Serine Endopeptidases
D004792:Enzyme Precursors; D002403:Cathepsins; D010450:Endopeptidases; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D012083:Renin