The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast
The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast
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DOI：
10.4049/jimmunol.175.12.7989
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发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Levi-Schaffer, F
中科院分区：
文献类型：
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作者：
Bachelet, I;Munitz, A;Levi-Schaffer, F
肥大细胞介导的反应可能受到激活信号和抑制信号之间的相互作用的调节。我们筛选了人脐带血肥大细胞中最近表征的 NK 细胞上表达的抑制性受体。我们发现 Ig 超家族成员 lRp60 在人类肥大细胞上表达。油 NK 细胞、IRp60 交联导致体外对靶细胞的细胞毒活性受到抑制。 IRp60 在肥大细胞上组成型表达，但在体外被嗜酸性粒细胞蛋白主要碱性蛋白和嗜酸性粒细胞衍生的神经毒素下调。免疫复合物介导的 IRp60 交联通过涉及酪氨酸磷酸化、磷酸酶募集和细胞钙内流终止的机制抑制 IgE 诱导的脱颗粒和干细胞因子介导的存活。为了评估 IRp60 在调节体内过敏反应中的作用，使用了过敏性腹膜炎小鼠模型，其中 IRp60 的小鼠同源物 LMIR1 在 BALB/c 小鼠中被单克隆抗体中和。这种中和导致炎症介质的释放和嗜酸性粒细胞浸润显着增加。这些数据证明了调节人类肥大细胞功能和过敏反应的新途径，表明 IRp60 作为未来治疗过敏和肥大细胞相关疾病的候选靶点。
Mast cell-mediated responses are likely to be regulated by the cross talk between activatory and inhibitory signals. We have screened human cord blood mast cells for recently characterized inhibitory receptors expressed on NK cells. We found that lRp60, an Ig superfamily member, is expressed on human mast cells. Oil NK cells, IRp60 cross-linking leads to the inhibition of cytotoxic activity vs target cells in vitro. IRp60 is constitutively expressed on mast cells but is down-regulated in vitro by the eosinophil proteins major basic protein and eosinophil-derived neurotoxin. An immune complex-mediated cross-linking of IRp60 led to inhibition of IgE-induced degranulation and stem cell factor-mediated survival via a mechanism involving tyrosine phosphorylation, phosphatase recruitment, and termination of cellular calcium influx. To evaluate the role of IRp60 in regulation of allergic responses in vivo, a murine model of allergic peritonitis was used in which the murine homolog of IRp60, LMIR1, was neutralized in BALB/c mice by mAbs. This neutralization led to a significantly augmented release of inflammatory mediators and eosinophilic infiltration. These data demonstrate a novel pathway for the regulation of human mast cell function and allergic responses, indicating IRp60 as a candidate target for future treatment of allergic and mast cell-associated diseases.