Patry C, Herbelin A, Lehuen A, Bach J F, Monteiro R C
Institut National de la Santé et de la Recherche Médicale, Unité 25, Hôpital Necker, Paris, France.
Immunology. 1995 Sep;86(1):1-5.
The functional capacity of the human monocyte receptor for the Fc portion of IgA (Fc alpha R) in mediating signal transduction was evaluated by cytokine release. F(ab')2 fragments of anti-Fc alpha R monoclonal antibodies (mAb) were used as specific probes to induce release of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Multivalent cross-linking by a secondary anti-mouse antibody [F(ab')2 fragments] induced a significant release of TNF-alpha and IL-6 by human blood mononuclear cells, indicating requirements for Fc alpha R aggregation on the cell surface to transmit signals. Both cytokines were released exclusively by adherent cells, identifying monocytes as the responding cells within the mononuclear cell population. This cytokine release could not be due to contaminating endotoxins, because it was not abolished by polymyxin B, a lipopolysaccharide (LPS) inhibitor. Moreover, purified recombinant soluble Fc alpha R inhibited the anti-Fc alpha R mAb-mediated cytokine release from blood monocytes, demonstrating that TNF-alpha and IL-6 were released in a receptor-specific manner. Our data suggest that Fc alpha R, through its capacity to mediate secretion of IL-6, may play an important role in B-cell proliferation and immunoglobulin production. On the other hand, release of TNF-alpha following stimulation of Fc alpha R molecules directly implicates these receptors in amplification and regulation of the inflammatory process occurring during IgA-mediated host defence.
通过细胞因子释放评估人单核细胞IgA Fc段受体（FcαR）介导信号转导的功能能力。抗FcαR单克隆抗体（mAb）的F（ab'）2片段用作特异性探针，以诱导肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的释放。用二抗[F（ab'）2片段]进行多价交联可诱导人血单核细胞显著释放TNF-α和IL-6，表明细胞表面FcαR聚集对于传递信号是必需的。两种细胞因子均仅由贴壁细胞释放，确定单核细胞是单核细胞群体中的反应细胞。这种细胞因子释放不可能是由于内毒素污染，因为它不会被脂多糖（LPS）抑制剂多粘菌素B消除。此外，纯化的重组可溶性FcαR抑制抗FcαR mAb介导的血单核细胞细胞因子释放，表明TNF-α和IL-6是以受体特异性方式释放的。我们的数据表明，FcαR通过其介导IL-6分泌的能力，可能在B细胞增殖和免疫球蛋白产生中起重要作用。另一方面，FcαR分子刺激后TNF-α的释放直接表明这些受体参与IgA介导的宿主防御过程中发生的炎症过程的放大和调节。
