The CD14⁺/CD16⁺ subset of human blood monocytes, which expresses low levels of the lipopolysaccharide receptor CD14 and high levels of the Fc receptor CD16 and exhibits features of mature tissue macrophages, is expanded in certain inflammatory conditions and may be relevant in atherosclerosis. Scavenger receptors (ScR) are important for lipid accumulation into macrophage-derived foam cells in atherogenesis and for the clearance of pathogens. Hence, we compared the function and expression of ScR in CD33^low CD16⁺ and CD33^high CD14⁺⁺ monocyte subsets. Double immunofluorescence analysis of isolated monocytes revealed that the CD33^low subset showed lower specific, ScR-mediated binding of DiI-labeled modified low-density lipoproteins (LDL) than CD33^high cells. Differences in modified LDL binding between subsets were accompanied by changes in mRNA expression. RT-PCR in sorted cells indicated lower ScR class A type I/II (ScR-AI/II) mRNA levels in CD14⁺/CD16⁺ than in CD14⁺⁺ cells, whereas CD36 transcripts were unaltered. This was paralleled by findings in mostly CD16⁺ monocyte-derived macrophages showing a marked reduction in ScR-mediated binding of acetylated LDL, but not in the binding of oxidized LDL, and lower expression of ScR-AI/II mRNA, but not CD36 transcripts, after exposure to tumor necrosis factor- for 48 h in vitro. Thus the subset of CD14⁺/CD16⁺ monocytes shows distinct ScR function and expression, possibly reflecting a preactivation by cytokines with a predilection for specific inflammatory or vascular conditions, e.g., atherogenesis.

atherogenesis; scavenger receptors; monocytes; oxidized low-density lipoproteins

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