Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B
Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B
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DOI：
10.1172/jci12195
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发表时间：
2001-10-01
影响因子：
15.9
通讯作者：
Kubagawa, H
中科院分区：
文献类型：
--
作者：
Uehara, T;Bléry, M;Kubagawa, H
在小鼠骨髓源性肥大细胞中评估了配对的激活型（PIR-A）和抑制性（PIR-B）受体对IgE抗体介导的过敏反应的修饰潜力。尽管肥大细胞同时产生PIR-A和PIR-B，但PIR-B被发现优先表达在细胞表面，在那里它被组成型酪氨酸磷酸化并与细胞内SHP-1蛋白酪氨酸磷酸酶相关。PIR-B与IgE受体（Fc epsilon RI）结合抑制IgE介导的肥大细胞活化和血清素的释放。令人惊讶的是，PIR-B的抑制活性在shp -1缺陷肥大细胞中没有受损。第三种基于酪氨酸的功能性抑制基序，即不能结合SHP-1、SHP-2和SHIP磷酸酶的基序，在对携带Fc epsilon ri的大鼠嗜碱性白血病（RBL）细胞的平行研究中被发现，这些细胞转染了PIR-B细胞质区突变的构建体。这些结果确定了PIR-B分子在肥大细胞上的优先表达，以及可以通过不依赖于shp -1的途径介导的抑制潜力。
The potential of the paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) types for modifying an IgE antibody-mediated allergic response was evaluated in mouse bone marrow-derived mast cells. Although mast cells produced both PIR-A and PIR-B, PIR-B was found to be preferentially expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with intracellular SHP-1 protein tyrosine phosphatase. PIR-B coligation with the IgE receptor (Fc epsilon RI) inhibited IgE-mediated mast cell activation and release of serotonin. Surprisingly, the inhibitory activity of PIR-B was unimpaired in SHP-1-deficient mast cells. A third functional tyrosine-based inhibitory motif, one that fails to bind the SHP-1, SHP-2, and SHIP phosphatases, was identified in parallel studies of Fc epsilon RI-bearing rat basophilic leukemia (RBL) cells transfected with constructs having mutations in the PIR-B cytoplasmic region. These results define the preferential expression of the PIR-B molecules on mast cells and an inhibitory potential that can be mediated via a SHP-1-independent pathway.