title: A chemotactic S100 peptide enhances scavenger receptor and Mac-1 expression and cholesteryl ester accumulation in murine peritoneal macrophages in vivo.
abstract: In the early development of atherosclerotic plaque, monocytes are recruited to the arterial intima where they accumulate lipid and become foam cells. The recently described murine chemotactic S100 protein, CP-10, may have an important role in this process. Intraperitoneal injection of CP-10(42-55) (chemotactic hinge region peptide) into mice caused a sustained leukocyte recruitment with a sixfold increase in monocyte numbers over 24 h. CP-10(42-55)--elicited monocyte/macrophages accumulated significantly increased cholesteryl esters in response to acetylated LDL, both in vivo and in vitro and this was associated with a twofold increase in scavenger receptor expression. By contrast, thioglycollate- and macrophage colony-stimulating factor-elicited macrophages expressed levels of scavenger receptor similar to those on resident macrophages and did not exhibit enhanced acetylated LDL loading in vitro. The leukocyte integrin Mac-1 (CD11b/CD18) and its beta subunit (CD18), but neither lymphocyte function-associated antigen-1 nor very late activation antigen-4, were upregulated on monocyte/macrophages elicited by CP-10(42-55), thioglycollate, and macrophage colony-stimulating factor. Cholesteryl ester accumulation in vitro was significantly enhanced by adhesion, which appeared to involve macrophage activation via ligation of Mac-1. The initial events of monocyte recruitment and adhesion to the vessel wall may be important in macrophage foam cell development, and CP-10 or related S100 proteins may contribute to the early inflammatory events of atherogenesis by stimulating these events.
authors.affiliation: Heart Research Institute, Camperdown, New South Wales, Australia.
authors.forename: W
authors.initials: W
authors.lastname: Lau
authors.forename: J M
authors.initials: JM
authors.lastname: Devery
authors.forename: C L
authors.initials: CL
authors.lastname: Geczy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018845:CD11 Antigens / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000494:pharmacology; D051122:Scavenger Receptors, Class B
chemical_list: D018845:CD11 Antigens; D018821:CD18 Antigens; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D016173:Macrophage Colony-Stimulating Factor