Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human FcεRI+ cells through interaction with the κ light chains of IgE
Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human FcεRI+ cells through interaction with the κ light chains of IgE
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DOI：
10.4049/jimmunol.170.4.1854
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发表时间：
2003-02-15
影响因子：
4.4
通讯作者：
Marone, G
中科院分区：
文献类型：
--
作者：
Genovese, A;Borgia, G;Marone, G
大消化链球菌蛋白 L 是一种与毒力相关的多结构域细菌表面蛋白。它由多达 5 个同源 Ig 结合域 (B1-B5) 组成，与 Ig kappa L 链的可变域相互作用。完整的 Protein L 在体外刺激人嗜碱性粒细胞合成和释放 IL-4 和 IL-13。覆盖 Ig 结合域 B1-B4 的 L 蛋白片段也诱导嗜碱性粒细胞释放 IL-4 和 IL-13。蛋白 L 诱导的 IL-4 释放最大百分比与抗 IgE 诱导的最大百分比 IL-4 释放之间以及完整蛋白 L 与 B1-B4 片段之间（r(s) = 0.90；p < 0.01）之间存在极好的相关性（r(s) = 0.82；p < 0.001）。去除与嗜碱性粒细胞结合的 IgE 显着减少抗 IgE、蛋白 L 和 B1-B4 诱导的 IL-4 释放。嗜碱性粒细胞与蛋白 L 或抗 IgE 预孵育导致对随后异源刺激的攻击完全交叉脱敏。从骨髓瘤患者 PS 和 PP（A 链）中纯化的 IgE 可以阻断抗 IgE 诱导的 IL-4 释放，但不能阻断蛋白 L 的释放活性。相反，从骨髓瘤患者 ADZ（κ 链）中纯化的 IgE 可以阻断抗 IgE 和蛋白 L 诱导的分泌。环孢菌素 A（而非环孢菌素 H）抑制蛋白 L 诱导的嗜碱性粒细胞释放 IL-4 和 IL-13。因此，蛋白 L 作为细菌 Ig 超抗原，通过与 IgE 同种型的 K L 链相互作用，诱导嗜碱性粒细胞合成和释放 IL-4 和 IL-13。
Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1-B5) that interact with the variable domain of Ig kappa L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1-B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (r(s) = 0.82; p < 0.001) between the maximal percent IL-4 release induced by protein L and that induced by anti-IgE and between intact protein L and the B1-B4 fragment (r(s) = 0.90; p < 0.01). Removal of IgE bound to basophils markedly reduced the IL-4 release induced by anti-IgE, protein L, and B1-B4. Preincubation of basophils with protein L or anti-IgE caused complete cross-desensitization to subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (A chains) blocked anti-IgE-induced IL-4 release, but not the releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with K L chains of the IgE isotype.