Caspase-independent cell death by MAIR-V (CD300LF), Ig-like receptor on myeloid cells

• Published in: Nihon Rinsho Men'eki Gakkai Sokai Shorokushu Vol. 37; p. 101
• Main Authors: 小田, ちぐさ, 渋谷, 和子, 本多, 伸一郎, 中埜, 貴子, 人見, 香織, 渋谷, 彰, ジャン, イスマイル, 田原, 聡子
• Format: Journal Article
• Language: Japanese
• Published: 日本臨床免疫学会 2009; The Japan Society for Clinical Immunology
• Subjects: apoptosis; CD300LF; MAIR-V
• ISSN: 1880-3296
• DOI: 10.14906/jscisho.37.0.101.0

We have recently identified paired activating and inhibitory receptors, MAIR (myeloid-associated immunoglobulin-like receptor) -I and -II, expressed on myeloid cell lineage (Yotsumoto et al, J Exp Med, 2003. Okoshi et al, Int Immunol, 2005. Nakahashi et al, J Immunol, 2006). MAIR-I and MAIR-II are members of a multigene family consisting of at least 9 genes on a small segment of mouse chromosome 11 (Nakano et al, Mol Immunol, 2007). Here we investigate the functional characteristics of MAIR-V (CD300LF), which contains two immunoreceptor tyrosine-based inhibitory motifs (ITIM) and an immunoreceptor tyrosine-based switching motif (ITSM) in its cytoplasmic region. To examine the role of MAIR-V, we generated anti-MAIR-V monoclonal antibodies. Cross-linking MAIR-V expressed on BW5147 with the immune complex of anti-MAIR-V with a secondary antibody significantly induced death, as determined by flow cytometry. However, we observed neither DNA fragmentation nor cell death was blocked by a caspase inhibitor, z-VAD fmk. Cross-linking the MAIR-V mutated at three tyrosines in the ITIMs and ITSM (Y-F241, 289, 325) still induced cell death, however, MAIR-V mutant lacking cytoplasmic region did not show cell death. Thus, the caspase-independent cell death induced by cross-linking MAIR-V is dependent on cytoplasmic region of MAIR-V other than ITIM or ITSM.