SHIP1是肥大细胞增生、细胞因子生成和过敏性炎症的抑制因子：体内试验研究
2009/08/11
SHIP1能通过水解PI3K产物磷脂酰肌醇3,4,5三磷酸，形成磷脂酰肌醇3,4二磷酸，抑制免疫受体信号。在体外试验中，SHIP1可以抑制FcepsilonRI及细胞因子介导的肥大细胞活化，但关于SHIP1在体内肥大细胞中的功能，以及Ship1(-/-)小鼠对肥大细胞相关疾病的易感性研究较少。
本研究在Ship1(-/-)小鼠中观察到系统性肥大细胞增生，血清IL-6、TNF和IL-5水平增加，以及过敏反应增强等现象。此外，通过应用Ship1(+/+)或Ship1(-/-)肥大细胞来重建存在肥大细胞缺陷的小鼠，我们发现上述缺陷由肥大细胞SHIP1缺失导致。另外，研究还发现，应用Ship1(-/-)肥大细胞重建的小鼠较应用Ship1(+/+)肥大细胞重建的小鼠具有更严重的过敏性哮喘的病理学特征。
结果显示， SHIP1能在体内抑制过敏性炎症和肥大细胞增生，这些作用对肥大细胞尤为明显。
（林江涛 审校）
Haddon DJ, et al. J Immunol. 2009 Jul 1;183(1):228-236.
SHIP1 Is a repressor of mast cell hyperplasia, cytokine production, and allergic inflammation in vivo.
Haddon DJ, Antignano F, Hughes MR, Blanchet MR, Zbytnuik L, Krystal G, McNagny KM.
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
SHIP1 inhibits immune receptor signaling through hydrolysis of the PI3K product phosphatidylinositol 3,4,5-trisphosphate, forming phosphatidylinositol 3,4-bisphosphate. In mast cells, SHIP1 represses FcepsilonRI- and cytokine-mediated activation in vitro, but little is known regarding the function of SHIP1 in mast cells in vivo or the susceptibility of Ship1(-/-) mice to mast cell-associated diseases. In this study, we found that Ship1(-/-) mice have systemic mast cell hyperplasia, increased serum levels of IL-6, TNF, and IL-5, and heightened anaphylactic response. Further, by reconstituting mast cell-deficient mice with Ship1(+/+) or Ship1(-/-) mast cells, we found that the above defects were due to loss of SHIP1 in mast cells. Additionally, we found that mice reconstituted with Ship1(-/-) mast cells suffered worse allergic asthma pathology than those reconstituted with Ship1(+/+) mast cells. In summary, our data show that SHIP1 represses allergic inflammation and mast cell hyperplasia in vivo and exerts these effects specifically in mast cells.
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哮喘患者和非哮喘患者在患有慢性上颌窦炎时的细菌定植和粒细胞活化
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鼻病毒与哮喘发生
