Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin-like receptor on myeloid cells.
The myeloid-associated Ig-like receptor family (CD300) consists of nine activating or inhibitory cell surface receptors preferentially expressed on myeloid cells and are encoded by the genes in a small cluster on mouse chromosome 11. One of the receptors, CD300LF (MAIR-V), has a long cytoplasmic tail containing two consensus ITIMs and an immunoreceptor tyrosine-based switching motif, suggesting that CD300LF regulates the activation of myeloid cells. However, the functional characteristics of this receptor are still incompletely understood. In this study, we demonstrate that cross-linking CD300LF with anti-CD300LF mAb induced cell death in peritoneal macrophages as well as in several transfectants expressing CD300LF. CD300LF-mediated cell death was dependent on the cytoplasmic region but did not require an ITIM or immunoreceptor tyrosine-based switching motif. Scanning electron microscopy revealed a loss of blebs from the surface of the dead cells mediated by CD300LF, a morphological feature similar to that observed in apoptotic cells. However, CD300LF-mediated cell death was not inhibited by a caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, or autophagy inhibitors, 3-methyladenine or N-acetyl-L-cystein. Moreover, the splicing isoform of a transcription factor, X-box binding protein-1, which is produced in dead cells as a response to endoplasmic reticulum stress, was not detected. Together, these results indicate that CD300LF mediates caspase and endoplasmic reticulum stress-independent cell death by a novel mechanism.
Can
Ismail
I
Department of Immunology, Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Tahara-Hanaoka
Satoko
S
Hitomi
Kaori
K
Nakano
Takako
T
Nakahashi-Oda
Chigusa
C
Kurita
Naoki
N
Honda
Shin-ichiro
S
Shibuya
Kazuko
K
Shibuya
Akira
A
D000111:Acetylcysteine / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001343:Autophagy; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors
D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; C482560:CLM-1 protein, mouse; D061945:Caspase Inhibitors; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; C426824:benzyloxycarbonyl-valyl-alanyl-(methyl)aspartic acid fluoromethyl ketone; D020169:Caspases; D000111:Acetylcysteine