Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily

被引:167
作者
Miyazaki, T
Hirokami, Y
Matsuhashi, N
Takatsuka, H
Naito, M
机构
[1] Basel Inst Immunol, CH-4005 Basel, Switzerland
[2] Univ Tokyo, Fac Med, Dept Internal Med 3, Bunkyo Ku, Tokyo 1138655, Japan
[3] Niigata Univ, Sch Med, Dept Pathol 2, Niigata 9518510, Japan
关键词
apoptosis; scavenger receptor cysteine-rich; macrophage; inhibitory factor; knockout mouse;
D O I
10.1084/jem.189.2.413
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Apoptosis of cells must be regulated both positively and negatively in response to a variety of stimuli in the body. Various environmental stresses are known to initiate apoptosis via differential signal transduction cascades. However, induction of signals that may inhibit apoptosis is poorly understood, although a number of intracellular molecules that mediate inhibition of apoptosis have been identified. Here we present a novel murine macrophage-specific 54-kD secreted protein which inhibits apoptosis (termed AIM, for apoptosis inhibitor expressed by macrophages). AIM belongs to the macrophage scavenger receptor cysteine-rich domain superfamily (SRCR-SF), members of which share a highly homologous conserved cysteine-rich domain. In AIM-deficient mice, the thymocyte numbers were diminished to half those in wild-type mice, and CD4/CD8 double-positive (DP) thymocytes were strikingly more susceptible to apoptosis induced by both dexamethasone and irradiation in vivo. Recombinant AIM protein significantly inhibited cell death of DP thymocytes in response to a variety of stimuli in vitro. These results indicate that in the thymus, AIM functions in trans to induce resistance to apoptosis within DP cells, and thus supports the viability of DP thymocytes before thymic selection.
引用
收藏
页码:413 / 422
页数:10
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