Platelet-enhanced apolipoprotein E production by human macrophages: a possible role in atherosclerosis.
Cholesterol-loaded human monocyte-derived macrophages increase their production of apolipoprotein E (apoE). Although cholesterol loading is often achieved with modified plasma lipoproteins, macrophages can be loaded also by coculture with platelets. Therefore, the relationship between platelet-mediated cholesteryl ester accumulation and apoE secretion was examined. Macrophages were isolated by adherence and cultured for 6 days in serum-free medium. Secreted apoE was measured with a sensitive solid-phase radioimmunoassay. Maximum apoE secretion by the adherent macrophages from 5 x 10(6) peripheral blood mononuclear cells was obtained with 3 x 10(8) platelets and was ten-fold greater than control cells cultured in the absence of platelets. Platelet-mediated apoE secretion was consistently greater than that obtained by culture with either native or acetylated low density lipoproteins. Whereas the 1000 g supernatants of unstimulated platelets were poor inducers of apoE secretion, substances rich in cholesterol that were shed from thrombin-stimulated platelets and recovered in the 1000 g supernatants were almost as active as intact platelets. In all studies, platelet-induced secretion of apoE paralleled the capacity of platelets to induce macrophage cholesterol accumulation, indicating that macrophage apoE secretion was readily influenced by macrophage cholesterol metabolism.
Takagi
Y
Y
Research Institute of Scripps Clinic, Department of Immunology, La Jolla, CA 92037.
Dyer
C A
CA
Curtiss
L K
LK
D001057:Apolipoproteins E / Q000097:blood*; D001161:Arteriosclerosis / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; D002784:Cholesterol; D008715:Methionine; D013917:Thrombin