The granulocyte-angiotensin system. Angiotensin I-converting activity of cathepsin G.
Cathepsin G, an Mr = 26,000-29,000 cationic human neutrophil lysosomal serine protease, releases angiotensin II from angiotensinogen and was, therefore, examined for angiotensin I-converting activity. Cathepsin G-dependent angiotensin I conversion was detected by a high performance liquid chromatography assay which permitted independent quantitation of angiotensin I and angiotensin II and detection of angiotensin degradation products. 1.8-5.0 X 10(-9) M cathepsin G converted angiotensin I (3.3 X 10(-4) M) to angiotensin II without further degradation of angiotensin II. The pH optimum for cathepsin G-catalyzed angiotensin I conversion was pH 7.0-7.5, and the Km and Kcat were 2.2 X 10(-4) M and 3.4 s-1, respectively. In contrast to dipeptidyl hydrolase-converting enzyme, cathepsin G did not inactivate bradykinin, did not cleave hippuryl-His-Leu, and was not inhibited by 10(-4) M Captopril or SQ 20881. Purified human neutrophils stimulated with 2.5 X 10(-6) M-10(-10) M fMet-Leu-Phe released angiotensin-converting activity with a Km of 3.3 X 10(-4) M. That the angiotensin-converting activity released from neutrophils was attributable to cathepsin G was indicated by similar susceptibility to inhibitors and adsorption by goat antibody to cathepsin G. The granulocyte-angiotensin system provides a mechanism for the local generation of angiotensin II at sites of neutrophil accumulation and may be of significance in regulation of blood flow in tissue microvasculature.
D000803:Angiotensin I; D056649:Cathepsin G; D002403:Cathepsins / Q000097:blood*; D002630:Chemotactic Factors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases
D002630:Chemotactic Factors; D009842:Oligopeptides; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000803:Angiotensin I; D002403:Cathepsins; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G