Generation of macrophage migration inhibitory activity by plasminogen activators.

Abstract

Medium from cultures of SV-40 transformed mouse [fibroblast] 3T3 cells (SV3T3) inhibits the migration in vitro of peritoneal exudate cells (macrophages) from guinea pigs while medium from untransformed 3T3 cultures does not. The generation of migration inhibitory factor (MIF)-like activity for peritoneal exudate cells from guinea pigs after incubation of a serum-free harvest fluid from SV3T3 cells with guinea pig serum is described. Inhibited macrophages lose a densely staining material from the cell surface coat compared with uninhibited guinea pig peritoneal exudate cells. The factor in SV3T3 harvest fluids which generates the migration inhibitory activity appears to be plasminogen activator, i.e., a serine protease, because plasminogen activator activity and the factor which generates MIF-like activity copurify and cochromatograph on Sephadex G-200 columns, and plasminogen activator activity and capacity to generate MIF-like activity are simultaneously lost on treatment with [3H]diisopropylflurophosphate. A purified preparation of a known plasminogen activator, human urokinase, can also generate MIF-like activity on reaction with guinea pig serum. Because transformation of 3T3 cells by SV-40 increases their plasminogen activator secretion, enhanced secretion of plasminogen activator by SV3T3 cells may explain why formation of MIF-like activity is observed in SV3T3 but not 3T3 cultures. A biochemical pathway was revealed whereby a product secreted by virus-transformed cells affected 1 function of a cell central to the host''s immunological defense system.