胞外酶 E-NPP3 通过嗜碱性粒细胞和肥大细胞负调控 ATP 依赖性慢性过敏反应。
The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.
机构信息
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
出版信息
Immunity. 2015 Feb 17;42(2):279-293. doi: 10.1016/j.immuni.2015.01.015.
Crosslinking of the immunoglobulin receptor FcεRI activates basophils and mast cells to induce immediate and chronic allergic inflammation. However, it remains unclear how the chronic allergic inflammation is regulated. Here, we showed that ecto-nucleotide pyrophosphatase-phosphodiesterase 3 (E-NPP3), also known as CD203c, rapidly induced by FcεRI crosslinking, negatively regulated chronic allergic inflammation. Basophil and mast cell numbers increased in Enpp3(-/-) mice with augmented serum ATP concentrations. Enpp3(-/-) mice were highly sensitive to chronic allergic pathologies, which was reduced by ATP blockade. FcεRI crosslinking induced ATP secretion from basophils and mast cells, and ATP activated both cells. ATP clearance was impaired in Enpp3(-/-) cells. Enpp3(-/-)P2rx7(-/-) mice showed decreased responses to FcεRI crosslinking. Thus, ATP released by FcεRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity.
免疫球蛋白受体 FcεRI 的交联激活嗜碱性粒细胞和肥大细胞，引发即刻和慢性过敏炎症。然而，慢性过敏炎症如何调节仍不清楚。在这里，我们发现 E-NPP3（也称为 CD203c）在 FcεRI 交联后迅速被诱导，可负调控慢性过敏炎症。与血清 ATP 浓度升高相关，Enpp3(-/-) 小鼠中的嗜碱性粒细胞和肥大细胞数量增加。Enpp3(-/-) 小鼠对慢性过敏病理高度敏感，这种敏感性可通过 ATP 阻断降低。FcεRI 交联诱导嗜碱性粒细胞和肥大细胞分泌 ATP，ATP 可激活这两种细胞。Enpp3(-/-) 细胞中的 ATP 清除受损。Enpp3(-/-)P2rx7(-/-) 小鼠对 FcεRI 交联的反应性降低。因此，FcεRI 交联释放的 ATP 刺激嗜碱性粒细胞和肥大细胞进一步激活，引发过敏炎症。E-NPP3 降低 ATP 浓度并抑制嗜碱性粒细胞和肥大细胞的活性。
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