INTRAPERITONEAL INJECTION OF PLATELET SECRETORY PRODUCTS INTO MICE INCREASES MACROPHAGE UPTAKE OF OXIDIZED LOW-DENSITY-LIPOPROTEIN

Oxidized low density lipoprotein (LDL) (Ox-LDL) is taken up by macroph ages at an enhanced rate and contributes to macrophage cholesterol acc umulation and foam cell formation. Platelet secretory products have be en shown to modulate the uptake of Ox-LDL by mouse peritoneal macropha ges. This study is unique since mouse peritoneal macrophages were inte racted with platelet conditioned medium (PCM, the supernatant that was obtained from collagen-treated washed human platelets) in the periton eal cavity of the mice rather than in plastic dishes. Macrophages obta ined from the peritoneal cavity of mice, 20 h after the injection of P CM (up to 30 mug of cholesterol/ml), demonstrated a substantial increm ent in the uptake of Ox-LDL. The effect of PCM demonstrated a dose- an d time-dependent pattern. The cellular uptake of the lipoprotein, meas ured as the cellular Ox-LDL degradation and cholesterol esterification rates, was increased by up to 60% and 30% respectively in macrophages collected from PCM-injected mice in comparison to control mice. These effects were the result of PCM-induced increased affinity of Ox-LDL t owards its receptor, and increased number of macrophage binding sites for Ox-LDL. Upon delipidation of PCM, only the protein fraction posses sed the ability to increase the cellular uptake of Ox-LDL. Dialyzed PC M, which is deprived of low molecular weight substances, still express ed the stimulatory effect of PCM. Our results thus suggest that a prot ein-like factor that is secreted from activated platelets can increase in vivo the ability of macrophages to take up Ox-LDL, as was also pre viously shown in in vitro studies.