Ligation of the FcRγ chain-associated human osteoclast-associated receptor enhances the proinflammatory responses of human monocytes and neutrophils
Ligation of the FcRγ chain-associated human osteoclast-associated receptor enhances the proinflammatory responses of human monocytes and neutrophils
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DOI：
10.4049/jimmunol.176.5.3149
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发表时间：
2006-03-01
影响因子：
4.4
通讯作者：
Bates, EEM
中科院分区：
文献类型：
--
作者：
Merck, E;Gaillard, C;Bates, EEM
我们之前已经描述了人类破骨细胞相关受体(HOSCAR)，表达在所有髓系细胞中，及其免疫功能。这种受体与FCR伽马链结合，传递激活信号，诱导单核细胞和树突状细胞的钙流动，并调节树突状细胞的特异性反应。在这项研究中，我们研究了Hoscar结扎对单核细胞和中性粒细胞的各种促炎反应的影响。经Hoscar结扎刺激的单核细胞释放IL-8/CXCL8和其他趋化因子，如上皮中性粒细胞激活肽-78/CXCL5、巨噬细胞衍生趋化因子/CCL22和MCP-1/CCL2，并上调参与细胞黏附和共刺激功能的标志物。在没有生存因素的情况下，通过Hoscar刺激的单核细胞寿命延长。虽然中性粒细胞的寿命没有受到影响，但当被Hoscar刺激时，这些细胞迅速释放活性氧中间体、脱颗粒乳铁蛋白、髓过氧化物酶和基质金属蛋白酶-9，并分泌IL-8/CXCL8。刺激2小时后，中性粒细胞表面分子表达发生改变，CD62L被切割，CD11b和CD66b表达增加。最后，我们证明了Hoscar和TLR配体在单核细胞和中性粒细胞上的协同作用，当Hoscar在脂多糖或R-848存在的情况下交联时，细胞因子的分泌增加了8倍。总体而言，我们的数据表明，Hoscar是单核细胞和中性粒细胞上的功能性受体，参与了初级促炎级联反应的诱导和下游免疫反应的启动。
We have previously described the human osteoclast associated receptor (hOSCAR), expressed in all cells of the myeloid lineage, and its immune functions. This receptor, which associates with the FcR gamma chain to transduce an activating signal, induces calcium flux in monocytes and dendritic cells, and modulates specific responses of dendritic cells. In this study, we have examined the effects of hOSCAR ligation on various proinflammatory responses of monocytes and neutrophils. Monocytes stimulated via hOSCAR ligation released IL-8/CXCL8 and other chemokines such as epithelial neutrophil-activating peptide-78/CXCL5, macrophage-derived chemokine/CCL22, and MCP-1/CCL2 and up-regulated markers involved in cell adhesion and costimulatory functions. Monocytes stimulated via hOSCAR in the absence of survival factors had an increased life span. Although the life span of neutrophils was unaffected, these cells, when stimulated via hOSCAR, rapidly released reactive oxygen intermediates, degranulated lactoferrin, myeloperoxidase, and matrix metalloproteinase-9 and also secreted IL-8/CXCL8. Neutrophils also underwent changes in cell surface molecule expression with the cleavage of CD62L and increased expression of CD11b and CD66b after 2-h stimulations. Finally, we demonstrated synergy between hOSCAR and TLR ligands on both monocytes and neutrophils, with up to 8-fold increases in cytokine secretion when hOSCAR was cross-linked in the presence of LPS or R-848. Overall, our data demonstrate that hOSCAR is a functional receptor on monocytes and neutrophils, involved in the induction of the primary proinflammatory cascade and the initiation of downstream immune responses.