Chemistry of a human monocyte-derived cell line (U937): identification of the angiotensin I-converting activity as leukocyte cathepsin G.
Angiotensin-converting enzyme, a dipeptidyl carboxypeptidase, catalyzes the conversion of angiotensin I to the vasoactive peptide angiotensin II. The finding of angiotensin-converting enzyme in dexamethasone-stimulated cultured monocytes and alveolar macrophages prompted the examination of a human monocyte-like cell line (U937) for angiotensin I-converting activity. Conversion of angiotensin I (5 X 10(-5) mol/L) to angiotensin II by U937 cell extracts (10(4) - 4 X 10(6) cells) was detected, and the pH optimum for the reaction was 7.0 to 8.0. The U937 cell angiotensin I-converting activity was purified to homogeneity by carboxymethylcellulose chromatography and trasylol affinity chromatography. The purified protein performed similarly to purified human neutrophil cathepsin G on sodium dodecyl sulfate-gradient polyacrylamide gel electrophoresis (SDS-gradient PAGE), elicited a reaction of complete identity with neutrophil cathepsin G when diffused against anti-cathepsin G antiserum, and had quantitatively similar angiotensin I-converting activity as neutrophil cathepsin G. Neutrophils and U937 cells had 143 and 52 times greater angiotensin I-converting capability than cultured monocytes or peripheral blood mononuclear cells, suggesting the relative importance of mobile cells containing cathepsin G in the local generation of angiotensin II. These data identify the angiotensin I-converting activity of the U937 cell as leukocyte cathepsin G and provide evidence that the U937 cell has neutrophil-like as well as monocyte-like characteristics.
Snyder
R A
RA
Kaempfer
C E
CE
Wintroub
B U
BU
D000806:Angiotensin-Converting Enzyme Inhibitors; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology* / Q000378:metabolism; D009504:Neutrophils; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012697:Serine Endopeptidases
D000806:Angiotensin-Converting Enzyme Inhibitors; D008222:Lymphokines; D003907:Dexamethasone; D002403:Cathepsins; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G