The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.
The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.
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DOI：
10.1016/j.immuni.2015.01.015
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发表时间：
2015-02
期刊：
影响因子：
32.4
通讯作者：
S. Tsai;M. Kinoshita;T. Kusu;H. Kayama;Ryu Okumura;K. Ikeda;Yosuke Shimada;A. Takeda;S. Yoshikawa;K. Obata-Ninomiya;Y. Kurashima;Shintaro Sato;E. Umemoto;H. Kiyono;H. Karasuyama;K. Takeda
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文献类型：
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作者：
S. Tsai;M. Kinoshita;T. Kusu;H. Kayama;Ryu Okumura;K. Ikeda;Yosuke Shimada;A. Takeda;S. Yoshikawa;K. Obata-Ninomiya;Y. Kurashima;Shintaro Sato;E. Umemoto;H. Kiyono;H. Karasuyama;K. Takeda
免疫球蛋白受体FcεRI的交联可激活嗜碱性粒细胞和肥大细胞，诱导速发型和慢性过敏性炎症。然而，目前尚不清楚慢性过敏性炎症是如何调节的。在这里，我们发现外核苷酸焦磷酸酶-磷酸二酯酶3（E-NPP 3），也称为CD 203 c，由FcεRI交联快速诱导，负调节慢性过敏性炎症。Enpp 3 −/−小鼠的嗜碱性粒细胞和肥大细胞数量随着血清ATP浓度的增加而增加。FcεRI交联诱导嗜碱性粒细胞和肥大细胞分泌ATP，ATP激活这两种细胞。Enpp 3 −/−细胞的ATP清除率受损，Enpp 3 −/− P2 rx 7 −/−小鼠对FcεRI交联的反应降低。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活化，引起过敏性炎症。E-NPP 3降低ATP浓度并抑制嗜碱性粒细胞和肥大细胞活性。
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 inEnpp3−/−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 inEnpp3−/−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.