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.