Journal of Lipid Research, Vol 29, 859-867, Copyright © 1988 by Lipid Research, Inc.
Platelet-enhanced apolipoprotein E production by human macrophages: a possible role in atherosclerosis
Y Takagi, CA Dyer and LK Curtiss
Research Institute of Scripps Clinic, Department of Immunology, La Jolla, CA 92037.
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.
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