Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with Fcgamma receptors and can be effectively blocked by decoy Fcgamma receptors.
Extravasations and emigration of neutrophils to the inflammatory site depend on the interaction of immune-complex with Fcgamma receptors and can be effectively blocked by decoy Fcgamma receptors.
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DOI：
10.1182/blood-2007-04-085944
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发表时间：
2008-01
期刊：
影响因子：
20.3
通讯作者：
R. Shashidharamurthy;R. Hennigar;S. Fuchs;P. Palaniswami;M. Sherman;P. Selvaraj
中科院分区：
文献类型：
--
作者：
R. Shashidharamurthy;R. Hennigar;S. Fuchs;P. Palaniswami;M. Sherman;P. Selvaraj
中性粒细胞外渗和迁移到炎症部位是许多抗体介导的自身免疫性疾病起始的重要早期步骤。细胞结合自身抗体或免疫复合物（IC）的Fc结构域能够通过补体和Fc γ R介导的机制触发中性粒细胞迁移。为了确定这2种途径在IC介导的中性粒细胞迁移中的临床相关性和相对贡献，我们用重组二聚体Fc受体CD 16 A-Ig中和了IC的Fc γ R结合活性，并研究了小鼠中IC诱导的炎症的早期事件。在逆转的Arthus反应中，全身给予纯化的CD 16 A-Ig可阻断IC诱导的炎症、肥大细胞脱粒和中性粒细胞外渗。尽管CD 16 A-Ig与IC的结合并没有改变IC的补体激活特性，但没有观察到补体依赖性中性粒细胞迁移的证据。这些结果表明，IC与炎症部位表达Fc γ R的细胞的相互作用导致化学引诱物的分泌，其介导该皮肤急性炎症模型中中性粒细胞的补体非依赖性迁移。此外，通过施用低亲和力Fc γ R的高亲合力Fc融合二聚体来阻断IC与炎性细胞上表达的Fc γ R的相互作用是预防自身免疫性疾病中IC诱导的急性炎症的有效方式。
Extravasation and emigration of neutrophils to the site of inflammation are essential early steps in the initiation of many antibody-mediated autoimmune diseases. The Fc domains of cell bound autoantibodies or immune-complexes (IC) are capable of triggering the neutrophil emigration via complement and FcgammaRs-mediated mechanisms. To define the clinical relevance and the relative contribution of these 2 pathways in IC-mediated neutrophil emigration, we have neutralized the FcgammaR-binding activity of IC with a recombinant dimeric Fc receptor, CD16A-Ig, and investigated the early events of IC-induced inflammation in mice. Systemic administration of purified CD16A-Ig blocked IC-induced inflammation, mast- cell degranulation, and extravasation of neutrophils in a reversed Arthus reaction. Although the binding of CD16A-Ig to IC did not alter the complement-activating properties of IC, no evidence for complement-dependent neutrophil emigration was observed. These results suggest that interaction of IC with cells expressing FcgammaRs at the inflammatory site results in the secretion of chemoattractants, which mediate complement-independent emigration of neutrophils in this cutaneous acute inflammation model. Furthermore, blocking the interaction of IC to FcgammaRs expressed on inflammatory cells by administering high-avidity Fc fusion dimers of low-affinity FcgammaRs is an effective way of preventing IC-induced acute inflammation in autoimmune diseases.