Increased synthesis of fibrinolytic inhibitor induced by muramyl dipeptide derivatives in human cultured endothelial cells

Effect of polymyxin B and colimycin on induction of plasminogen antiactivator by lipopolysaccharide in human endothelial cell culture

“…Incubation with colimycin alone did not change the basal inhibitory activity, Effect of polymyxin B on MDP-induced fibrinolytic inhibition. As described previously (6), MDP also stimulates the synthesis of fibrinolytic inhibitor in cultured endothelial cells. The susceptibility of this MDP effect to polymnyxin B therefore was determined ( Table 2).…”

“…Results of recent study indicated the generation by LPS of a fast-acting plasminogen ahtiactivator by human endothelial cells which could not be ddtected when cells were incubated in human albumin (4). Our previous results have shown that it is possible to stimulate, with MDP, production of inhibitor in the presence of 0.35% bovine albumin (6). Under these conditions LPS had no visible effect, but substitution of clinically injectable nonpyrogenic human albumin allowed detection of a clear stimulating activity of LPS.…”

“…The ability of these cells to synthesize inhibitor(s) of plasminogen activators has been demonstrated previously (7,10,12,22,28). Recently, we have observed that muramyl dipeptide (MDP), the immunoadjuvant properties of which have been well documented (3,20), could stimulate this fibrinolytic inhibitor synthesis (6). This led us to compare the sensitivity of the endothelial response toward LPS and MDP.…”

“…Inhibition of urokinase-induced fibrinolysis. Supernatants were mixed (1: 1, vol/vol) with 6 to:Z5 U of urokinase solution (Institut Choay, Paris, France)'per ml, and 30 ,ul of the mixture was deposited on a standard fibrin plate prepared with rich plasminogen bovine fibrinogen (Koch and Light Laboratories, Colnbrook, England) as described previously (6). The lysis area was measured after 18 h at 37°C.…”

Regulation of the Synthesis and Secretion of Plasminogen Activators by Endothelial Cells

“…Endothelial cells from bovine and human blood vessels produce large amounts of PAI-1 [14,15,79,82,91,96,105,145,146], The production of this inhibitor is markedly enhanced by bacterial lipopoly saccharide [147][148][149], muramyl dipeptide [150], the monokines interleukin 1 [149,[151][152][153] and tumor necrosis factor [154,155] , and thrombin [96,109]. Its activity is reduced by activated protein C [91,113] and by high concentrations of thrombin [91,156] , During the hours that the incubations of endothelial cells in vitro usually last, the ratio between the amount of PAs and the amount of PAI-1 determines the actual fibri nolytic activity in the conditioned medium.…”