Secretory IgA-mediated basophil activation. Its mechanisms and implication in allergy.

分泌型伊加（sIgA）是上气道和下气道中粘液分泌物中最丰富的IG同种型，其中嗜碱性粒细胞在变应性炎症期间发挥效应器功能。我们最近证明，在琼脂糖凝胶珠上固定的sIgA能够诱导嗜碱性粒细胞脱粒（约占总组胺的15%）。为了研究这种脱颗粒的详细机制，我们在这项研究中建立了一个新的检测系统sIgA介导的嗜碱性粒细胞活化。固定在塑料表面上的sIgA诱导强组胺释放（约50%的总组胺）与抗IgE，我们分析了嗜碱性粒细胞的信号转导的sIgA使用各种抑制剂的性质。百日咳毒素完全抑制sIgA诱导的嗜碱性粒细胞组胺释放，但不影响抗IgE诱导的释放。磷脂酰肌醇3-激酶（PI 3-kinase）抑制剂渥曼青霉素（wortmannin）也能抑制sIgA介导的释放。这些结果强烈表明，sIgA激活嗜碱性粒细胞通过IgE独立的新机制，涉及Gi蛋白和PI 3-激酶。

Secretory IgA (sIgA) is the most abundant Ig isotype in mucous secretions in the upper and lower airways, where basophils exert effector functions during allergic inflammation. We recently demonstrated that immobilized sIgA on Sepharose beads is capable of inducing basophil degranulation (〜15% of total histamine). To investigate the detailed mechanisms of this degranulation, we established in this study a new assay system for sIgA-mediated basophil activation. Immobilized sIgA on a plastic surface induced strong histamine release (〜50% of total histamine) comparable to anti-IgE, and we analyzed the nature of basophil signal transduction by sIgA using various inhibitors. sIgA-induced basophil histamine release was inhibited completely by pertussis toxin, but anti-IgE-induced release was not affected. sIgA-mediated release was also inhibited by phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, wortmannin. These results strongly suggest that sIgA activates basophils via an IgE-independent novel mechanism involving both Gi protein and PI 3-kinase.