title: Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42/44 and p38 mitogen-activated protein kinase pathways in the platelets.
abstract: Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the mechanism by which it induces high mortality remains unclear. We found that LT treatment could induce severe hemorrhage in mice and significantly suppress human whole-blood clotting and platelet aggregation in vitro. In addition, LT could inhibit agonist-induced platelet surface P-selectin expression, resulting in the inhibition of platelet-endothelial cell engagements. Data from Western blot analysis indicated that LT treatment resulted in the suppression of p42/44 and p38 mitogen-activated protein kinase pathways in platelets. Combined treatments with LT and antiplatelet agents such as aspirin and the RGD-containing disintegrin rhodostomin significantly increased mortality in mice. Our data suggest that platelets are a pathogenic target for anthrax LT.
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jyh-Hwa
authors.initials: JH
authors.lastname: Kau
authors.forename: Der-Shan
authors.initials: DS
authors.lastname: Sun
authors.forename: Wei-Jern
authors.initials: WJ
authors.lastname: Tsai
authors.forename: Huey-Fen
authors.initials: HF
authors.lastname: Shyu
authors.forename: Hsin-Hsien
authors.initials: HH
authors.lastname: Huang
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Lin
authors.forename: Hsin-Hou
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000737:chemistry*; D001427:Bacterial Toxins / Q000633:toxicity*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D014774:Virulence; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases