Anthrax lethal toxin: a weapon of multisystem destruction

Lethal toxin (LT) is a major virulence factor secreted by anthrax bacteria. It is composed of two proteins, PA (protective antigen) and LF (lethal factor). PA transports the LF inside the cell, where LF, a zinc-dependent metalloprotease cleaves the mitogen activated protein kinase kinase (MAPKK) enzymes of the mitogen activated protein kinase (MAPK) signaling pathway, thereby impairing their function. This disruption of the MAPK pathway, which serves essential functions such as proliferation, survival and inflammation in all cell types, results in multisystem dysfunction in the host. The inactivation of the MAPK pathway in both macrophages and dendritic cells leads to inhibition of proinflammatory cytokine secretion, downregulation of costimulatory molecules such as CD80 and CD86, and ineffective T cell priming. The net result is an impaired innate and adaptive immune response. Endothelial cells of the vascular system undergo apoptosis upon LT exposure, also likely due to inactivation of the MAPK pathway. The activity of various hormone receptors such as glucocorticoids, progesterone and estrogen is also blocked, due to inhibition of p38 MAPK phosphorylation, thus affecting the bodys response to stress. The present review summarizes the various disarming effects of Bacillus anthracis through the use of a single weapon, the lethal toxin.Received 12 June 2004; received after revision 13 July 2004; accepted 28 July 2004     

结核分枝杆菌分泌蛋白调控巨噬细胞自噬诱导持续性感染

巨噬细胞的自噬作用能够保护宿主抵抗结核分枝杆菌的感染;而持续性感染的MTB(Mycobacterium tuberculosis)可以从自噬体中逃逸或抑制自噬的发生,从而在宿主体内长期存活。尽管相关机制不明确,但胞内存活的MTB分泌蛋白在持续性感染时发挥了重要作用。它可以通过抑制巨噬细胞自噬维持蛋白质稳定性和在胞内长期存活,导致LTBI(latent TB infection)的发生。综述了MTB的四种分泌蛋白(Eis、Pkn G、Sap M和Hsp16. 3)在持续性感染中调节巨噬细胞自噬的作用,可能为发现LTBI新的生物标志物和药物新靶点提供有效思路。     

载脂蛋白E-基因敲除鼠VLDL和IDL在动脉硬化中的作用

探讨载脂蛋白Ｅ（ａｐｏＥ）－基因敲除鼠极低密度脂蛋白（ＶＬＤＬ）和中间密度脂蛋白（ＩＤＬ）组分（ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ）致动脉硬化作用．采用超离法从ａｐｏＥ－基因敲除鼠血浆中分离ＶＬＤＬ和ＩＤＬ组分,与鼠腹腔巨噬细胞共育,观察ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ与巨噬细胞的相互作用．ＡｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ导致细胞胆固醇酯含量显著增加．其诱导的细胞［３Ｈ］胆固醇油酸脂量高达１５．１ｎｍｏｌ／ｍｇ细胞蛋白,是天然低密度脂蛋白的８．４倍．形态学观察显示,经ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ处理的巨噬细胞与苏丹黑Ｂ呈阳性染色．细胞结合实验表明,１２５Ｉ－ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ与巨噬细胞的总结合可被非标记配基取代８０％以上,特异结合呈一饱和图形．同时细胞缔合和细胞内降解实验也显示相似结果．非修饰的ａｐｏＥｋｏ－ＶＬＤＬ／ＩＤＬ可通过一特异而不依赖于ａｐｏＥ的途径导致巨噬细胞胆固醇酯的显著蓄积     

中性红染料摄入法检测人肺泡巨噬细胞吞噬活性探讨

本文作者对中性红染料摄入法的实验条件──肺泡灌洗细胞贴壁时间选择；摄入中性红时间对吞噬活性的影响，及细胞数量时吞噬活性的影响作了探讨．并对肺癌患者肺泡巨噬细胞吞噬活性作了检测．结果表明，此方法用于检测人肺泡巨噬细胞吞噬活性不但指标客观、准确，而且操作简便、省时、微量，适于大量样本检测．