Novel properties of human monocyte plasminogen activator.
Human peripheral monocytes stimulated by either muramyl dipeptide [N-acetyl-muramoyl-L-alanyl-D-isoglutamine], bacterial lipopolysaccharide or lymphokine-containing supernatants of human lymphocytes, could be shown to produce and secrete appreciable activities of a 52 000-Mr plasminogen activator. This enzyme was suppressed in control and stimulated cultures by dexamethasone (0.1 microM). Monocyte plasminogen activator could only be assayed under conditions of low ionic strength and had no detectable activity at 0.15 M NaCl. Intracellular enzyme was present as a proenzyme, requiring activation by preincubation with plasminogen containing traces of plasmin, before its activity could be seen on sodium dodecyl sulphate/polyacrylamide gel electrophoresis by a fibrin overlay method. Secreted enzyme was in the active form. Further incubation of lysate or supernatant plasminogen activator with plasminogen did not produce any active enzyme species of Mr 36 000, unlike incubations of urokinase with plasminogen. Moreover, comparisons with other plasminogen activators of Mr 52 000 from transformed cell lines showed that the monocyte activator was unique in its resistance to monocyte minactivin, a specific inactivator of urokinase-type plasminogen activators, and in its sensitivity to human alpha 2-macroglobulin. It was therefore concluded that human monocyte plasminogen activator, although sharing an Mr of 52 000 in common with other such activators, is not identical to the high Mr form of urokinase or the plasminogen activators of transformed cells. On present evidence it is the least likely of these enzymes to be active extracellularly under normal physiological conditions.
D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004058:Diffusion; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000097:blood* / Q000145:classification; D015849:Plasminogen Inactivators; D013053:Spectrophotometry; D013379:Substrate Specificity; D000511:alpha-Macroglobulins / Q000494:pharmacology
D015849:Plasminogen Inactivators; D000511:alpha-Macroglobulins; D010960:Plasminogen Activators