Secretory IgA induces antigen-independent eosinophil survival and cytokine production without inducing effector functions
Secretory IgA induces antigen-independent eosinophil survival and cytokine production without inducing effector functions
复制标题
DOI：
10.1016/j.jaci.2005.07.014
复制
发表时间：
2005-10-01
影响因子：
14.2
通讯作者：
Kita, H
中科院分区：
文献类型：
--
作者：
Barternes, KR;Cooper, KM;Kita, H
背景：嗜酸性粒细胞存在于人体组织中，尤其是胃肠道和气道炎症的粘膜组织中。分泌型伊加（Secretory IgA，S-IgA）是这些组织分泌的主要抗体，可能在先天性免疫应答中发挥作用。目的：由于嗜酸性粒细胞和S-IgA经常共存于粘膜组织中，我们研究了无抗原的S-IgA对人嗜酸性粒细胞的存活、基因表达和效应功能的潜在调节作用。将嗜酸性粒细胞与不含抗原的溶液中的S-IgA（可溶性S-IgA）或与固定的S-IgA一起孵育以模拟多价抗原交联。通过超氧阴离子生成和脱粒监测嗜酸性粒细胞活化。在24至96小时之间评估存活率。基因芯片和ELISA检测基因和蛋白表达。嗜酸性粒细胞裂解液进行了检查，通过免疫印迹细胞外信号调节激酶（ERK）phosphorylation.Results：固定S-IgA刺激嗜酸性粒细胞超氧化物的产生和脱粒;可溶性S-IgA没有。虽然固定化S-IgA抑制嗜酸性粒细胞的生存在体外，可溶性S-IgA提高生存，这涉及自分泌生产的GM-CSR可溶性S-IgA无抗原诱导的各种细胞因子，趋化因子，信号转导分子，抗凋亡因子和细胞表面标志物的mRNA水平的增加。通过使用ELISA，我们证实了所选介质的蛋白质表达。Eos与可溶性S-IgA的相互作用可能涉及FcciRI（CD 89）和ERK通路的激活。结论：不含多价抗原的分泌型伊加可能调节Eos的存活和基因表达。粘膜组织中的嗜酸性粒细胞可以被不同形式的S-IgA激活（细胞因子产生和存活）或完全激活（脱粒和超氧化物释放）。
Background: Eosinophils in human beings reside in tissues, especially the mucosal tissues of the gastrointestinal tract and inflamed airways. Secretory IgA (S-IgA) is the predominant antibody secreted by these tissues and likely plays a role in the innate immune response.Objective: Because eosinophils and S-IgA are often colocalized in mucosal tissues, we examined the potential regulatory effects of S-IgA without antigens on survival, gene expression, and effector functions of human eosinophils.Methods: Eosinophils were incubated with S-IgA in solution without antigens (soluble S-IgA) or with S-IgA immobilized to mimic multivalent antigen cross-linking. Eosinophil activation was monitored by superoxide anion generation and degranulation. Survival was assessed between 24 and 96 hours. Gene and protein expression were examined by microarray and ELISA. Eosinophil lysates were examined by immunoblot for extracellular signal-regulated kinase (ERK) phosphorylation.Results: Immobilized S-IgA stimulated eosinophil superoxide production and degranulation; soluble S-IgA did not. Although immobilized S-IgA inhibited eosinophil survival in vitro, soluble S-IgA enhanced survival; this involved autocrine production of GM-CSR Soluble S-IgA without antigens induced increases in mRNA levels of various cytokines, chemokines, signal transduction molecules, antiapoptotic factors, and cell surface markers. By using ELISA, we confirmed protein expression of selected mediators. Eosinophil interaction with soluble S-IgA likely involves FcciRI (CD89) and ERK pathway activation.Conclusion: Secretory IgA without multivalent antigens may regulate survival and gene expression of eosinophils. Eosinophils in mucosal tissues can be either primed for action (cytokine production and survival) or fully activated (degranulation and superoxide release) by different forms of S-IgA.