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【科普】肿瘤坏死因子拮抗剂影响巨噬细胞应答
NEW YORK (Reuters Health) Jan 02 - Tumor necrosis factor (TNF) blockers interfere with the macrophage response to Mycobacterium tuberculosis by suppressing maturation of phagosomes, according to a report in the December 15th issue of The Journal of Infectious Diseases.
It's known that anti-TNF therapy for autoimmune diseases, including rheumatoid arthritis, increases the risk of reactivation of latent tuberculosis, but the mechanisms underlying this have yet to be elucidated, the authors explain.
Dr. James Harris from St. James's Hospital and Trinity College Dublin, Ireland, and colleagues investigated the effects of adalimumab, infliximab, and etanercept on the responses of macrophages to infection with mycobacteria in vitro.
They focused on phagosome maturation, because this process is essential for the presentation of mycobacterial antigens to T cells and the initiation of adaptive immune responses.
All three TNF blockers inhibited phagosome maturation in THP-1 cells pretreated with interferon-gamma for 24 hours or infected with M. tuberculosis, the authors report.
Similarly, adalimumab and infliximab (but not etanercept) inhibited phagosome maturation in primary human peripheral blood monocyte-derived macrophages, while having no effect on uptake of mycobacteria by macrophages.
Adalimumab, infliximab, and etanercept inhibited interferon-gamma induced phagosome acidification in THP-1 cells, the researchers note, whereas treatment of cells with TNF-alpha directly stimulated phagosome acidification in both THP-1 cells and primary human monocyte-derived macrophages.
"These results suggest a role for TNF-alpha in activating phagosome maturation and highlight a mechanism through which TNF-alpha blockade can affect the host response to mycobacteria," the authors conclude.
肿瘤坏死因子拮抗剂影响巨噬细胞应答TB
（纽约路透电）1月2日-12月15日传染病杂志的一份报告显示，肿瘤坏死因子（TNF）阻断剂通过抑制吞噬小体成熟干扰巨噬细胞应答结核分枝杆菌。
据了解，抗肿瘤坏死因子治疗自身免疫性疾病包括类风湿性关节炎，增加潜伏结核病复发之风险，但其机制尚未阐明，作者解释。
爱尔兰圣詹姆士医院和都柏林三一学院詹姆斯-哈里斯博士和他的同事调查了阿达木单抗、英夫利昔单抗和依那西普对巨噬细胞体外应答结核分枝杆菌感染的影响。
他们侧重于吞噬体的成熟，因为这个过程是向T细胞递呈分枝杆菌抗原和启动适应性免疫反应必不可少的。
作者报告，三种肿瘤坏死因子受体阻滞剂抑制了γ-干扰素预处理24小时或结核菌感染的THP-1细胞吞噬体成熟。
同样，阿达木单抗和英夫利昔单抗（但不包括依那西普）抑制了人外周血原代单核细胞衍生的巨噬细胞吞噬体成熟，但不影响巨噬细胞摄取结核分枝杆菌。
研究人员注意到，阿达木单抗、英夫利昔单抗和依那西普抑制了γ-干扰素诱导的THP-1细胞吞噬体酸化，而TNFα直接刺激THP-1细胞和人外周血原代单核细胞衍生的巨噬细胞吞噬体酸化。
“这些结果表明TNF-α在激活吞噬体成熟的作用，强烈提示TNF-α阻断能影响宿主应答分枝杆菌反应”，作者总结。
J Infect Dis 2008;198:1842-1850. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-02-24 17:12
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