Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adapters DAP12 and FcRγ chain on peritoneal macrophages
Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adapters DAP12 and FcRγ chain on peritoneal macrophages
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DOI：
10.4049/jimmunol.178.2.765
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发表时间：
2007-01-15
影响因子：
4.4
通讯作者：
Shibuya, Akira
中科院分区：
文献类型：
--
作者：
Nakahashi, Chigusa;Tahara-Hanaoka, Satoko;Shibuya, Akira
在骨髓细胞上表达的某些活化免疫受体与DAP 12或Fc γ RI γ（FcR γ链）（携带ITAM的跨膜衔接蛋白）非共价结合。一种活化受体，骨髓相关Ig样受体（MAIR）II，在小鼠脾和腹腔中的B细胞和巨噬细胞亚群上表达，并与这些细胞中的DAP 12相关。然而，我们在此证明MAIR-II与mAb的交联诱导了显著量的炎性细胞因子TNF-α和IL-6从DAP 12（-/-）以及野生型（WT）腹膜巨噬细胞的分泌。我们发现MAIR-II不仅与DAP 12相关，而且与腹腔巨噬细胞中的FcR γ链同源二聚体相关。LPS增强MAIR-II的FcR γ链表达和FcR γ链依赖性细胞表面表达，并对MAIR-II介导的腹腔巨噬细胞炎性细胞因子分泌具有累加效应。MAIR-II跨膜区的赖氨酸残基参与与FcR-γ链以及DAP 12的缔合。我们的研究结果提出了第一例使用DAP 12或FcRC γ链作为信号适配器的活化受体。FcR-y链可以在腹腔巨噬细胞的MAIR-II介导的炎症反应中提供与DAP 12的合作和/或对DAP 12的补偿。
Certain activating immune receptors expressed on myeloid cells noncovalently associate with either DAP12 or Fc epsilon RI gamma (FcR gamma chain), the ITAM-bearing transmembrane adapter proteins. An activating receptor, myeloid-associated Ig-like receptor (MAIR) II, is expressed on a subset of B cells and macrophages in the spleen and peritoneal cavity of mice and associates with DAP12 in these cells. However, we demonstrate here that cross-linking MAIR-II with mAb induced secretion of a significant amount of the inflammatory cytokines TNF-alpha and IL-6 from DAP12(-/-) as well as wild-type (WT) peritoneal macrophages. We show that MAIR-II associates with not only DAP12 but also FcR gamma chain homodimers in peritoneal macrophages. LPS enhanced the FcR gamma chain expression and FcR gamma chain-dependent cell surface expression of MAIR-II and had additive effects on MAIR-II-mediated inflammatory cytokine secretion from peritoneal macrophages. The lysine residue in the transmembrane region of MAIR-II was involved in the association with FcR-y chain as well as DAP12. Our findings present the first case of an activating receptor that uses either DAP12 or FcRC gamma chain as a signaling adapter. The FcR-y chain may provide cooperation with and/or compensation for DAP12 in MAIR-II-mediated inflammatory responses by peritoneal macrophages.