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 macrophages at an enhanced rate and contributes to macrophage cholesterol accumulation and foam cell formation. Platelet secretory products have been shown to modulate the uptake of Ox-LDL by mouse peritoneal macrophages. This study is unique since mouse peritoneal macrophages were interacted with platelet conditioned medium (PCM, the supernatant that was obtained from collagen-treated washed human platelets) in the peritoneal cavity of the mice rather than in plastic dishes. Macrophages obtained from the peritoneal cavity of mice, 20 h after the injection of PCM (up to 30 micrograms of cholesterol/ml), demonstrated a substantial increment in the uptake of Ox-LDL. The effect of PCM demonstrated a dose- and time-dependent pattern. The cellular uptake of the lipoprotein, measured 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 towards its receptor, and increased number of macrophage binding sites for Ox-LDL. Upon delipidation of PCM, only the protein fraction possessed the ability to increase the cellular uptake of Ox-LDL. Dialyzed PCM, which is deprived of low molecular weight substances, still expressed the stimulatory effect of PCM. Our results thus suggest that a protein-like factor that is secreted from activated platelets can increase in vivo the ability of macrophages to take up Ox-LDL, as was also previously shown in in vitro studies.
Hussein
O
O
Lipid Research Unit, Rambam Medical Center, Haifa, Israel.
Brook
G J
GJ
Aviram
M
M
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001685:Biological Factors / Q000378:metabolism / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D017077:Culture Media, Conditioned; D003956:Dialysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004951:Esterification; D005487:Foam Cells / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D010084:Oxidation-Reduction; D015539:Platelet Activation
D001685:Biological Factors; D017077:Culture Media, Conditioned; D008077:Lipoproteins, LDL; D002784:Cholesterol