Differential chemokine receptor expression and function in human monocyte subpopulations

作者：Christian Weber, Kai-Uwe Belge, Philipp von Hundelshausen, Georg Draude, Birgit Steppich, Mathias Mack, Marion Frankenberger, Kim S. C. Weber, H W Löms Ziegler-Heitbrock · 发表于：Journal of Leukocyte Biology · 年份：2000 · DOI：10.1002/jlb.67.5.699 · 被引用次数：404 · 研究领域：Chemokine receptors and signaling、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

The subset of human blood monocytes expressing low levels of CD14 and high levels of CD16 (CD14+CD16+) exhibits features resembling mature tissue macrophages and can be expanded in inflammatory conditions. We analyzed expression of CC chemokine receptors (CCR) in CD14+CD16+ versus CD14++ monocytes, which may be crucial for specific trafficking. Multicolor flow cytometric analysis of whole peripheral blood revealed that, as opposed to CD14++ monocytes, the CD14+CD16+ subset lacked surface expression of monocyte chemotactic protein-1 (MCP-1) receptor CCR2, however, it showed significantly higher surface expression of the macrophage inflammatory protein 1alpha (MIP-1alpha)/RANTES receptor CCR5. This was paralleled by differences in mRNA expression in the subsets, as shown by reverse transcriptase-polymerase chain reaction using sorted cells. In comparison to CD14++ monocytes, CD14+CD16+ cells expressed lower CCR2 but higher CCR5 transcript levels, whereas CCR1 levels were equivalent. Flow cytometric analysis of isolated human monocytes recovered after transendothelial chemotaxis assays revealed that the percentage of CD14+CD16+ cells was dramatically reduced in the fraction migrating toward MCP-1 compared with the fraction that did not migrate or the input, showing that polarized CCR2 expression was accompanied by a differential chemotactic responsiveness. Moreover, CD11b surface expression was preferentially up-regulated by MCP-1 in CD14++ cells but by MIP-1alpha in CD14+CD16+ ...