Monocyte chemoattractant protein-1 induces scavenger receptor expression and monocyte differentiation into foam cells.
Accumulation of monocytes and the entrapment of oxidized-low-density lipoprotein (ox-LDL) in monocytes are important in the differentiation into "foam" macrophages and the pathogenesis of atherosclerosis. We investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the expression of scavenger receptor (SCR) by using resting monocytes prepared by counterflow centrifugal elutriation. Our results showed that: (1) MCP-1 increased the expression of CD36 SCR by flow cytometric analysis. (2) MCP-1 increased incorporation of 125I-labeled ox-LDL and oil red O staining. (3) MCP-1 and ox-LDL enhanced in vitro transendothelial monocyte migration. (4) These functions were mediated at least in part via extracellular signal-regulated kinase (ERK) pathway. (5) MCP-1 and ox-LDL did not induce monocyte proliferation. Our results imply that MCP-1 is involved in the inflammatory process of atherosclerosis through the induction of SCR expression via the ERK pathway and differentiation of monocytes into foam macrophages, as well as induction of monocyte migration.
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 807-8555, Japan.
Takahiro
T
Tabata
Shinichiro
S
Mine
Chie
C
Kawahara
Yosuke
Y
Okada
Yoshiya
Y
Tanaka
D018955:CD36 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005487:Foam Cells / Q000166:cytology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein