A CHEMOTACTIC S100 PEPTIDE ENHANCES SCAVENGER RECEPTOR AND MAC-1 EXPRESSION AND CHOLESTERYL ESTER ACCUMULATION IN MURINE PERITONEAL-MACROPHAGES IN-VIVO

In the early development of atherosclerotic plaque, monocytes are recr uited to the arterial intima where they accumulate lipid and become fo am cells, The recently described murine chemotactic S100 protein, CP-1 0, may have an important role in this process, Intraperitoneal injecti on 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 macroph ages accumulated significantly increased cholesteryl esters in respons e 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 ma crophages expressed levels of scavenger receptor similar to those on r esident macrophages and did not exhibit enhanced acetylated LDL loadin g in vitro, The leukocyte integrin Mac-1 (CD11b/CD18) and its beta sub unit (CD18), but neither lymphocyte function-associated antigen-1 nor very late activation antigen-4, were upregulated on monocyte/macrophag es elicited by CP-10(42.55), thioglycollate, and macrophage colony-sti mulating factor, Cholesteryl ester accumulation in vitro was significa ntly enhanced by adhesion, which appeared to involve macrophage activa tion via ligation of Mac-1, The initial events of monocyte recruitment and adhesion to the vessel wall may be important in macrophage foam c ell development, and CP-10 or related S100 proteins may contribute to the early inflammatory events of atherogenesis by stimulating these ev ents.