Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adapters DAP12 and FcRgamma chain on peritoneal macrophages.
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.
Nakahashi
Chigusa
C
Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Tahara-Hanaoka
Satoko
S
Totsuka
Naoya
N
Okoshi
Yasushi
Y
Takai
Toshiyuki
T
Ohkohchi
Nobuhiro
N
Honda
Shin-Ichiro
S
Shibuya
Kazuko
K
Shibuya
Akira
A
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
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