Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation.
A role for immune and inflammatory processes in the induction of atherosclerotic lesions is emerging. These studies were undertaken to determine whether activation by lipopolysaccharide (LPS) enhances the ability of macrophages to become foam cells. Since LPS activation inhibits scavenger receptor activity, we studied the ability of LPS-activated RAW 264.7 macrophages to accumulate lipid from a variety of lipid particles that are not ligands for the scavenger receptor. Macrophages activated by LPS, in the absence of lipid particles, accumulated triglyceride, but not cholesterol ester (CE). The addition of Soyacal, a triglyceride-rich particle, further enhanced this LPS-stimulated triglyceride accumulation. LPS activation similarly enhanced CE accumulation almost 3-fold from two CE-rich lipoproteins, beta VLDL and LDL, as compared with controls. The unstimulated control cells only accumulated significant CE from beta VLDL and not LDL. LPS-enhanced lipid accumulation was dependent on LPS dose and began after 8-12 h of incubation. LPS increased the degradation of 125I-labelled LDL and the cell-associated 125I-labelled LDL at 37 degrees C by 1.8-fold. Degradation remained saturable, consistent with a receptor-mediated process. Antioxidants did not inhibit LPS-induced CE accumulation from LDL. Thus, activation of RAW 264.7 macrophages enhanced their ability to accumulate lipid from a variety of lipid particles and to become foam cells. These data suggest a potential role for infections, and LPS in particular, in atherogenesis.
Funk
J L
JL
Department of Medicine, University of California, San Francisco 94121.
Feingold
K R
KR
Moser
A H
AH
Grunfeld
C
C
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000502:physiology*; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D014280:Triglycerides / Q000378:metabolism
D008070:Lipopolysaccharides; D014280:Triglycerides; D002784:Cholesterol