Monoclonal antibodies against macrophage colony-stimulating factor diminish the number of circulating intermediate and nonclassical (CD14 ++CD16 +/CD14 +CD16 ++) monocytes in rheumatoid arthritis patient

摘要

Human blood monocytes are divided into 3 subsets: classical (CD14++CD16~-), intermediate (CD14++CD16+), and nonclassi-cal (CD14+CD16++).1 The latter 2 subpopulations produce inflammatory cytokines in response to a wide variety of pattern receptor ligands and are constantly surveying the endothelium for signs of inflammation or damage, whereas classical ones are the main producers of anti-inflammatory IL-10.2 There appears to be a developmental relationship between these cells (from classical by intermediates to nonclassical), and the presence of macrophage colony-stimulating factor (M-CSF) seems to be crucial for their differentiation.3'4 It has been recently shown in the mouse model that antibody-blocking M-CSF receptor (R) depletes the nonclassical monocytes, tissue and tumor-associated macrophages.5 In addition, targeted disruption of the M-CSFR gene resulted in profound mononuclear phagocyte deficiency in mice.6 However, there is no direct evidence that blockade of M-CSF/M-CSFR axis in humans inhibits maturation or survival of any circulating monocyte subpopulation.