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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.
AuthorsW Lau, J M Devery, C L Geczy
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 95 Issue 5 Pg. 1957-65 (May 1995) ISSN: 0021-9738 [Print] United States
PMID7738161 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD11 Antigens
  • CD18 Antigens
  • Cholesterol Esters
  • Lipoproteins, LDL
  • Macrophage-1 Antigen
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Recombinant Proteins
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Macrophage Colony-Stimulating Factor
Topics
  • Amino Acid Sequence
  • Animals
  • CD11 Antigens (biosynthesis)
  • CD18 Antigens (biosynthesis)
  • Cholesterol Esters (metabolism)
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Inflammation
  • Lipoproteins, LDL (isolation & purification, metabolism)
  • Macrophage Colony-Stimulating Factor (pharmacology)
  • Macrophage-1 Antigen (biosynthesis)
  • Macrophages, Peritoneal (cytology, drug effects, physiology)
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptide Fragments (pharmacology)
  • Receptors, Immunologic (biosynthesis)
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Recombinant Proteins (pharmacology)
  • Scavenger Receptors, Class B

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