Heparin stimulation of plasminogen activator secretion by macrophage‐like cell line raw264.7: Role of the scavenger receptor

Abstract

Secretion of urokinase‐type plasminogen activator (uPA) by RAW264.7 cells was stimulated by heparin in a dose‐ and time‐dependent manner. Secretion of uPA was not detected when cells were exposed to heparin at 4°C, indicating that heparin was not simply releasing receptor‐bound uPA. Furthermore, prior removal of membrane‐associated uPA did not influence heparin's ability to stimulate the release of uPA from the macrophage‐like line. Low molecular weight and weakly anticoagulant heparins stimulated uPA secretion but less effectively than other heparin fractions. The observed stimulation in macrophage uPA secretion by heparin is similar to that previously reported for polyanions recognized by the scavenger receptor including fucoidan, polyinosinic acid, dextran sulfate, and acetyl‐LDL (Falcone and Ferenc: J. Cell. Physiol. 135: 387–396, 1988). Evidence that heparin's binding to RAW264.7 cells is mediated by the scavenger receptor is derived from experiments in which fucoidan blocked the specific binding of [³H]‐heparin to RAW264.7 cells. However, heparin partially inhibited the stimulation of cholesteryl [³H]‐oleate synthesis observed in these cells upon incubation with acetyl‐LDL and weakly inhibited cellular binding of ¹²⁵l‐acetyl‐LDL at 4°C. These data indicate that heparin's binding to RAW264.7 cells is mediated, only in part, by the scavenger receptor. Nonetheless, neither heparin nor fucoidan was able to stimulate the release of plasminogen activator activity from monocyte‐like U937 cells which are devoid of scavenger receptor activity.