title: The effects of anthrax lethal toxin on host barrier function.
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 of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.
authors: 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. tao.xie@fda.hhs.gov
authors: Tao
authors: T
authors: Xie
authors: Roger D
authors: RD
authors: Auth
authors: David M
authors: DM
authors: Frucht
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology* / Q000473:pathology; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000378:metabolism / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000493:pharmacokinetics / Q000633:toxicity*; D018916:Blood-Aqueous Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin