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Dual Assemblies of an Activating Immune Receptor, MAIR-II, with ITAM-Bearing Adapters DAP12 and FcR Chain on Peritoneal Macrophages¹

Chigusa Nakahashi^*,, Satoko Tahara-Hanaoka^*, Naoya Totsuka^*, Yasushi Okoshi^*, Toshiyuki Takai^,, Nobuhiro Ohkohchi, Shin-ichiro Honda^*, Kazuko Shibuya^* and Akira Shibuya^2,*

^* Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences and Department of Surgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan; Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and Core Research for Evolutional, Science and Technology, Kawaguchi, Japan

Certain activating immune receptors expressed on myeloid cells noncovalently associate with either DAP12 or FcRI (FcR 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- 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 chain homodimers in peritoneal macrophages. LPS enhanced the FcR chain expression and FcR 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 chain as well as DAP12. Our findings present the first case of an activating receptor that uses either DAP12 or FcR chain as a signaling adapter. The FcR chain may provide cooperation with and/or compensation for DAP12 in MAIR-II-mediated inflammatory responses by peritoneal macrophages.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported in part by the grants provided by the Ministry of Education, Science and Culture of Japan.

² Address correspondence and reprint requests to Dr. Akira Shibuya. E-mail address: ashibuya{at}md.tsukuba.ac.jp

³ Abbreviations used in this paper: TM, transmembrane; PTK, protein tyrosine kinase; MAIR, myeloid-associated Ig-like receptor; WT, wild type; PEC, peritoneal exudate cell; TREM, triggering receptor expressed on myeloid cell.

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