Sepsis-induced apoptosis of the thymocytes in mice.

胸腺细胞 细胞凋亡 生物 微生物学 肿瘤坏死因子α 坏死 分子生物学 CD8型 铜绿假单胞菌 细菌 免疫学 免疫系统 生物化学 遗传学
作者
Shulhn-Der Wang,Kuen-Jeng Huang,Yee‐Shin Lin,Huan‐Yao Lei
出处
期刊:Journal of Immunology [The American Association of Immunologists]
卷期号:152 (10): 5014-5021 被引量:199
标识
DOI:10.4049/jimmunol.152.10.5014
摘要

Intraperitoneal injection of Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) induces thymic atrophy in mice. The thymus weight, cell number, and viability began to decrease at 3 h, and reached their lowest level at 72 h. The thymocyte death was associated with DNA fragmentation of approximately 200 base pairs in ladder form. The kinetic study on histopathology revealed the process of thymocyte death and thymic atrophy. Flow-cytometric analysis showed that CD4+CD8+ thymocytes decreased predominantly. LPS caused thymocyte apoptosis, but only in LPS-responder mice, unlike Gram-negative bacteria that induced apoptosis in both LPS-responder (C3H/HeN) and LPS-nonresponder (C3H/HeJ). Gram-positive bacteria Streptococcus pneumoniae also caused apoptosis in LPS-nonresponder (C3H/HeJ) and LPS-responder mice (B6). The kinetics of serum TNF-alpha production after Gram-negative or Gram-positive bacteria injection was slightly different. E. coli induced serum TNF-alpha peak at 1 h in B6 mice, whereas S. pneumoniae induced a peak at 6 h in C3H/HeJ and at 9 h in B6 mice. Similarly, S. pneumoniae induced thymocyte apoptosis around 9 to 12 h, which was 6 to 9 h later than that observed with E. coli in B6 mice. Anti-TNF-alpha Ab completely blocked the E. coli-induced thymocyte apoptosis, but was only partially inhibitory on the S. pneumoniae-induced thymocyte apoptosis. Furthermore, thymocyte apoptosis induced by E. coli was inhibited by cycloheximide or actinomycin D. These data indicate that both Gram-negative and Gram-positive bacteria could induce thymus atrophy via apoptosis, and that TNF-alpha is a common denominator released and might be responsible for the thymocyte apoptosis.
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