Chemokine receptor usage by human eosinophils - The importance of CCR3 demonstrated using an antagonistic monoclonal antibody
Chemokine receptor usage by human eosinophils - The importance of CCR3 demonstrated using an antagonistic monoclonal antibody
复制标题
DOI：
10.1172/jci119145
复制
发表时间：
1997-01-15
影响因子：
15.9
通讯作者：
Mackay, CR
中科院分区：
文献类型：
--
作者：
Heath, H;Qin, SX;Mackay, CR
趋化因子通过g蛋白偶联的7个跨膜受体结合并发出信号。各种趋化因子受体在白细胞上表达，这些可能使白细胞亚群选择性地归巢到炎症部位。人嗜酸性粒细胞表达eotaxin受体CCR3，但除eotaxin外，还对多种CC趋化因子有反应，包括RANTES、单核细胞趋化蛋白(MCP)-2、MCP-3和MCP-4。在这里，我们描述了一种mAb， 7B11，它对CCR3具有选择性，并具有真正受体拮抗剂的特性。7B11阻断了各种放射性标记趋化因子与CCR3转染物或嗜酸性粒细胞的结合。用该单抗预处理嗜酸性粒细胞可阻断所有CCR3配体诱导的趋化性和钙nu。在所有被检查的个体中，包括过敏和嗜酸性粒细胞供者，95%的嗜酸性粒细胞对eotaxin、RANTES、MCP-2、MCP-3和MCP-4的反应显示是通过CCR3介导的。IL-8受体，特别是CXCR2，在IL-5引发的嗜酸性粒细胞上被诱导，然而这些嗜酸性粒细胞对CC趋化因子的反应方式与未引发的嗜酸性粒细胞相同。这些结果证明了CCR3对嗜酸性粒细胞反应的重要性，以及完全拮抗该受体的可行性。
Chemokines bind and signal through G-protein coupled seven transmembrane receptors. Various chemokine receptors are expressed on leukocytes, and these may impart selective homing of leukocyte subsets to sites of inflammation. Human eosinophils express the eotaxin receptor, CCR3, but respond to a variety of CC chemokines apart from eotaxin, including RANTES, monocyte chemotactic protein (MCP)-2, MCP-3, and MCP-4. Here we describe a mAb, 7B11, that is selective for CCR3 and has the properties of a true receptor antagonist. 7B11 blocked binding of various radiolabeled chemokines to either CCR3 transfectants, or eosinophils. Pretreatment of eosinophils with this mAb blocked chemotaxis and calcium nu induced by all CCR3 ligands. In all individuals examined, including allergic and eosinophilic donors, > 95% of the response of eosinophils to eotaxin, RANTES, MCP-2, MCP-3, and MCP-4 was shown to be mediated through CCR3. The IL-8 receptors, particularly CXCR2, were induced on IL-5 primed eosinophils, however these eosinophils responded to CC chemokines in the same manner as unprimed eosinophils. These results demonstrate the importance of CCR3 for eosinophil responses, and the feasibility of completely antagonizing this receptor.