title: Activation of human prorenin by neutrophil elastase.
abstract: Although about 90% of human renin circulates as inactive prorenin, the mechanism of prorenin activation in vivo is not known. We found that human polymorphonuclear leukocytes (PMN) activate prorenin at a neutral pH. Prorenin was partially purified from human amniotic fluid, and its activation was measured by the release of angiotensin I from sheep angiotensinogen. In control experiments, thermolysin was the standard activator. PMN cells were separated from blood and, after N2 cavitation or degranulation by cytochalasin, were fractionated by differential centrifugation. Elastase and cathepsin G activities were determined with synthetic fluorescent substrates. The activators of prorenin concentrated in the azurophil granules were released by Triton; most of the activation was due to elastase. Elastase, purified from human PMN, activated prorenin completely. The activation by the granular fraction was inhibited 77% by a specific elastase inhibitor in the presence of a detergent, but only 22% by a cathepsin G inhibitor. After inhibition of elastase, the residual activity was inhibited by diisopropylfluorophosphate; thus, it was due to a serine protease(s) such as cathepsin G. We suggest that human renin fully activated by elastase may still contain an N-terminal pentapeptide fragment of the propeptide.
authors.affiliation: Department of Anesthesiology, University of Illinois College of Medicine, Chicago 60612.
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Maruta
authors.forename: B
authors.initials: B
authors.lastname: Wagner
authors.forename: X G
authors.initials: XG
authors.lastname: FA
authors.forename: H L
authors.initials: HL
authors.lastname: James
authors.forename: E G
authors.initials: EG
authors.lastname: Erdös
mesh_terms: D000653:Amniotic Fluid; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000502:physiology*; D012083:Renin / Q000096:biosynthesis / Q000502:physiology*; D013347:Subcellular Fractions / Q000502:physiology
chemical_list: D004792:Enzyme Precursors; D010196:Pancreatic Elastase; D012083:Renin