Distinct scavenger receptor expression and function in the human CD14(+)/CD16(+) monocyte subset

The CD14(+)/CD16(+) subset of human blood monocytes, which expresses low le vels of the lipopolysaccharide receptor CD14 and high levels of the Fc rece ptor CD16 and exhibits features of mature tissue macrophages, is expanded i n certain inflammatory conditions and may be relevant in atherosclerosis. S cavenger receptors (ScR) are important for lipid accumulation into macropha ge-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 anal ysis of isolated monocytes revealed that the CD33(low) subset showed lower specific, ScR-mediated binding of DiI-labeled modified low-density lipoprot eins (LDL) than CD33(high) cells. Differences in modified LDL binding betwe en 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 CD1 4(+)/CD16(+) than in CD14(+ +) cells, whereas CD36 transcripts were unalter ed. This was paralleled by findings in mostly CD16(+) monocyte-derived macr ophages showing a marked reduction in ScR-mediated binding of acetylated LD L, but not in the binding of oxidized LDL, and lower expression of ScR-AI/I I mRNA, but not CD36 transcripts, after exposure to tumor necrosis factor-a lpha for 48 h in vitro. Thus the subset of CD14(+)/CD16(+) monocytes shows distinct ScR function and expression, possibly reflecting a preactivation b y cytokines with a predilection for specific inflammatory or vascular condi tions, e.g., atherogenesis.