title: Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adapters DAP12 and FcRgamma chain on peritoneal macrophages.
abstract: Certain activating immune receptors expressed on myeloid cells noncovalently associate with either DAP12 or FcepsilonRIgamma (FcRgamma 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 FcRgamma chain homodimers in peritoneal macrophages. LPS enhanced the FcRgamma chain expression and FcRgamma 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 FcRgamma chain as well as DAP12. Our findings present the first case of an activating receptor that uses either DAP12 or FcRgamma chain as a signaling adapter. The FcRgamma chain may provide cooperation with and/or compensation for DAP12 in MAIR-II-mediated inflammatory responses by peritoneal macrophages.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Nakahashi
authors.forename: Satoko
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.forename: Naoya
authors.initials: N
authors.lastname: Totsuka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okoshi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Honda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D019281:Dimerization; D008070:Lipopolysaccharides / Q000494:pharmacology; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D019056:Receptors, Polymeric Immunoglobulin; C484963:Tyrobp protein, mouse; C517261:myeloid-associated Ig-like receptor, mouse; D008239:Lysine