Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin-like receptor on myeloid cells
Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin-like receptor on myeloid cells
复制标题
DOI：
10.4049/jimmunol.180.1.207
复制
发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Shibuya, Akira
中科院分区：
文献类型：
--
作者：
Can, Ismail;Tahara-Hanaoka, Satoko;Shibuya, Akira
骨髓相关 Ig 样受体家族 (CD300) 由 9 个优先在骨髓细胞上表达的激活或抑制性细胞表面受体组成，由小鼠 11 号染色体上的一个小簇中的基因编码。其中一种受体 CD300LF (MAIR-V) 具有长胞质尾部，其中包含两个共有 ITIM 和一个基于免疫受体酪氨酸的转换基序，表明 CD300LF 调节骨髓细胞的激活细胞。然而，该受体的功能特征仍不完全清楚。在本研究中，我们证明 CD30OLF 与抗 CD300LF mAb 交联可诱导腹膜巨噬细胞以及表达 CD300LF 的几种转染子中的细胞死亡。 CD300LF 介导的细胞死亡依赖于细胞质区域，但不需要 ITIM 或基于免疫受体酪氨酸的转换基序。扫描电子显微镜显示，CD300LF 介导的死细胞表面出现气泡丢失，这一形态特征与凋亡细胞中观察到的相似。然而，CD300LF介导的细胞死亡不受半胱天冬酶抑制剂N-苄氧羰基-Val-Ala-Asp-氟甲基酮或自噬抑制剂3-甲基腺嘌呤或N-乙酰基-L-半胱氨酸的抑制。此外，未检测到转录因子 X-box 结合蛋白-1 的剪接异构体，该转录因子是死细胞中对内质网应激的反应而产生的。总之，这些结果表明 CD300LF 通过一种新机制介导 caspase 和内质网应激独立的细胞死亡。
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 CD30OLF 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.