Regulation of plasminogen activator secretion in mouse peritoneal macrophages. II. Inhibition by immunomodulators of bacterial origin.

Two classes of immunomodulators of bacterial origin, peptidoglycan derivatives and lipopolysaccharides, are able to block in vitro the production of plasminogen activator by elicited macrophages: the release of the enzyme into the medium is inhibited and the intracellular activity reduced. In the case of peptidoglycan derivatives, high molecular weight compounds like WSA (water-soluble adjuvant) are stronger inhibitors than small molecules like MPP (muramyl pentapeptide). MDP (muramyl dipeptide) gives partial inhibition only. WSA (at 100 micrograms/ml) completely inhibits plasminogen activator production; the inhibition is reversible and specific. LPS is active at low concentrations (25-100 ng/ml). At concentrations higher than 50-100 ng/ml the action of LPS becomes irreversible and less specific. Peptidoglycan-derived immunomodulators can inhibit plasminogen activator production in the presence of polymixin B or in the case of macrophages obtained from C3H/HeJ mice; LPS is inactive under such conditions.