Modulation of plasminogen activator secretion by activated macrophages: influence of serum factors and correlation with tumoricidal potential.
A high molecular weight fraction of human serum (Fr-1) was found to both inhibit macrophage tumoricidal activity and enhance plasminogen activator activity in supernates over activated macrophages in vitro. Conversely, a 40- to 90-kilodalton serine esterase (Fr-3) also found in normal human serum and endotoxin enhanced tumoricidal potential and suppressed the supernatant plasminogen activator activity. Inactivation of either Fr-1 or Fr-3 by 2-mercaptoethanol or diisopropyl fluorophosphate, respectively, abolished both biologic effects. Examination of cell-associated and culture medium plasminogen activator activity before and after acidification to inactivate proteinase inhibitors indicated that suppression of plasminogen activator activity by Fr-3 or endotoxin most likely represents modulation of macrophage plasminogen activator secretion. The findings demonstrate that activated macrophages are capable of highly coordinated biologic responses to alterations in their microenvironment and suggest that it is in fact the high potential for such responsiveness that reliably characterizes the activated macrophage. The results also suggest that an endogenous regulatory system dependent on the interaction of serine esterases may operate to regulate the functional capabilities of activated macrophages.
D000818:Animals; D001769:Blood; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology; D010960:Plasminogen Activators / Q000378:metabolism*
D004731:Endotoxins; D004950:Esterases; D010960:Plasminogen Activators