the effects of anthrax lethal toxin on host barrier function炭疽致命的毒素对主机屏障功能的影响.pdf

Toxins 2011, 3, 591-607; doi:10.3390/toxins3060591 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review The Effects of Anthrax Lethal Toxin on Host Barrier Function Tao Xie, Roger D. Auth and David M. Frucht * Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA; E-Mails: tao.xie@ (T.X.); roger.auth2@ (R.D.A.) * Author to whom correspondence should be addressed; E-Mail: david.frucht@; Tel.: + 1-301-827-0720; Fax: + 1-301-827-0852. Received: 19 May 2011; in revised form: 2 June 2011 / Accepted: 7 June 2011 / Published: 14 June 2011 Abstract: The pathological actions of anthrax toxin require the activities of its edema factor (EF) and lethal factor (LF) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA). LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs), but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT) leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark o