AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice
AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice
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DOI：
10.1016/s0002-9440(10)63880-1
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发表时间：
2003-03-01
影响因子：
6
通讯作者：
Naito, M
中科院分区：
文献类型：
--
作者：
Kuwata, K;Watanabe, H;Naito, M
巨噬细胞表达的凋亡抑制因子（AIM）可抑制CD 4（+）CD 8（+）（CD 4/CD 8）双阳性胸腺细胞的凋亡，并支持这些细胞在胸腺选择中的生存能力。然而，已经提出AIM的多效性功能。本研究采用热灭活短棒杆菌（Corynebacterium parvum，C. parvum）注射到携带纯合突变（AIM（-/-））和野生型（AIM（+/+））小鼠的小鼠中，以研究AIM在肝肉芽肿形成中的作用。在AIM（-/-）小鼠中，肝肉芽肿的大小和数量比AIM（+/+）小鼠更大，并且肉芽肿的吸收更延迟。白细胞介素-12的产生在AIM（-/-）小鼠中比在AIM（+/+）小鼠中更显著。在AIIM（+/+）小鼠的肝脏中，注射小隐孢子虫后AIM信使核糖核酸（mRNA）的表达增加。原位杂交结果显示，AIM mRNA在肝脏枯否细胞和渗出液巨噬细胞中均有表达，尤其在肉芽肿中。AIM（-/-）小鼠肉芽肿中大量的T细胞和自然杀伤T（NKT）细胞发生凋亡，表明AIM阻止了小隐孢子虫诱导的炎症中NKT细胞和T细胞的凋亡。重组AIM（rAIM）蛋白在体外可显著抑制小隐孢子虫刺激的小鼠外周血NKT细胞和T细胞的凋亡。这些结果表明，AIM的功能是诱导NKT细胞和T细胞内的凋亡抗性，并支持肉芽肿性炎症中的宿主防御。
Apoptosis inhibitor expressed by macrophages (AIM) inhibits apoptosis of CD4(+)CD8(+) (CD4/CD8) double-positive thymocytes, and supports the viability of these cells on the thymic selection. However, pleiotropic functions of AIM have been suggested. In this study, heat-killed Corynebacterium parvum (C. parvum) was injected into mice carrying the homozygous; mutation (AIM(-/-)) and wild-type (AIM(+/+)) mice, to investigate the role of AIM in the formation of hepatic granulomas. In AIM(-/-) mice, the size and the number of hepatic granulomas were larger, and the resorption of granulomas was more delayed than in AIM(+/+) mice. The production of interleukin-12 was more prominent in AIM(-/-) mice than in AIM(+/+) mice. In the liver of AIIM(+/+) mice, expression of AIM messenger ribonucleic acid (mRNA) increased after C parvum injection. In situ hybridization demonstrated that AIM mRNA was expressed in Kupffer cells and exudate macrophages in the liver, especially in granulomas. Larger numbers of T cells and natural killer T (NKT) cells underwent apoptosis in the granulomas of AIM(-/-) mice, suggesting that AIM prevents apoptosis of NKT cells and T cells in C parvum-induced inflammation. Recombinant AIM (rAIM) protein significantly inhibited apoptosis of NKT cells and T cells obtained from C parvum-stimulated fivers in vitro. These results indicate that AIM functions to induce resistance to apoptosis within NKT cells and T cells, and supports the host defense in granulomatous inflammation.