title: Anthrax lethal and edema toxins fail to directly impair human platelet function.
abstract: Hemorrhage is a prominent clinical manifestation of systemic anthrax. Therefore, we have examined the effects of anthrax lethal and edema toxins on human platelets. We find that anthrax lethal toxin fails to cleave its target, mitogen-activated protein kinase 1, and anthrax edema toxin fails to increase intracellular cyclic adenosine monophosphate. Surface expression of toxin receptors tumor endothelial marker 8 and capillary morphogenesis gene 2, as well as coreceptor low density lipoprotein receptor-related protein 6 (LRP6), are markedly reduced, preventing toxin binding to platelets. Our studies suggest that the hemorrhagic clinical manifestations of systemic anthrax are unlikely to be caused by the direct binding and entry of anthrax toxins into human platelets.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL 32610-0277, USA.
authors.forename: Kassidy M
authors.initials: KM
authors.lastname: Chauncey
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Szarowicz
authors.forename: Gurjit S
authors.initials: GS
authors.lastname: Sidhu
authors.forename: Russell L
authors.initials: RL
authors.lastname: During
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Southwick
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D020869:Gene Expression Profiling; D006805:Human Experimentation; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D059748:Proteolysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018000:Receptors, Peptide
chemical_list: C473287:ANTXR1 protein, human; C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C030325:anthrax toxin; D000242:Cyclic AMP; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1