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

Distinct scavenger receptor expression and function in the human CD14+/CD16+ monocyte subset
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DOI:
10.1152/ajpheart.1999.276.4.h1144
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发表时间:
1999-04-01
影响因子:
4.8
通讯作者:
Weber, C
Weber, C
中科院分区:
医学2区
文献类型:
--
作者:
Draude, G;Von Hundelshausen, P;Weber, C

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人血液单核细胞的CD 14(+)/CD 16(+)亚群表达低水平的脂多糖受体CD 14和高水平的Fc受体CD 16,并表现出成熟组织巨噬细胞的特征,在某些炎症条件下扩增,可能与动脉粥样硬化相关。清道夫受体(ScR)在动脉粥样硬化形成中对脂质积聚到巨噬细胞源性泡沫细胞中以及对病原体的清除是重要的。因此,我们比较了ScR在CD 33(低)CD 16(+)和CD 33(高)CD 14(+)(+)单核细胞亚群中的功能和表达。分离的单核细胞的双重免疫荧光分析显示,CD 33(低)子集显示出较低的特异性,ScR介导的二碘标记的修饰的低密度脂蛋白(LDL)的结合比CD 33(高)细胞。亚群之间修饰LDL结合的差异伴随着mRNA表达的变化。分选细胞中的RT-PCR显示,与CD 14(+ +)细胞相比,CD 14(+)/CD 16(+)细胞中的ScR-AI/II mRNA水平较低,而CD 36转录本无变化。在体外暴露于肿瘤坏死因子-α 48 h后,大多数CD 16(+)单核细胞来源的巨噬细胞显示ScR介导的乙酰化LDL结合显著降低,但氧化LDL结合没有降低,ScR-AI/II mRNA表达降低,但CD 36转录物没有降低。因此,CD 14(+)/CD 16(+)单核细胞的亚群显示出不同的ScR功能和表达,可能反映了细胞因子的预活化,其偏好于特定的炎症或血管疾病,例如,动脉粥样硬化
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-alpha 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.