title: Soluble P-selectin rescues mice from anthrax lethal toxin-induced mortality through PSGL-1 pathway-mediated correction of hemostasis.
abstract: As one of the virulence factors of Bacillus anthracis, lethal toxin (LT) induces various pathogenic responses including the suppression of the coagulation system. In this study, we observed that LT markedly increased the circulating soluble P-selectin (sP-sel) levels and microparticle (MP) count in wild-type but not P-selectin (P-sel, Selp-/-) or P-sel ligand-1 (PSGL-1, Selplg-/-) knockout mice. Because sP-sel induces a hypercoagulable state through PSGL-1 pathway to generate tissue factor-positive MPs, we hypothesized that the increase in plasma sP-sel levels can be a self-rescue response in hosts against the LT-mediated suppression of the coagulation system. In agreement with our hypothesis, our results indicated that compared with wild-type mice, Selp-/-and Selplg-/-mice were more sensitive to LT. In addition, the recombinant sP-sel treatment markedly ameliorated LT-mediated pathogenesis and reduced mortality. As a result, elicitation of circulating sP-sel is potentially a self-rescue response, which is beneficial to host recovery from an LT-induced hypocoagulation state. These results suggest that the administration of sP-sel is likely to be useful in the development of a new strategy to treat anthrax.
authors.affiliation: a Department of Molecular Biology and Human Genetics , Tzu-Chi University , Hualien , Taiwan.|b Center for Vascular Medicine , Tzu-Chi University , Hualien , Taiwan.
authors.forename: Der-Shan
authors.initials: DS
authors.lastname: Sun
authors.affiliation: a Department of Molecular Biology and Human Genetics , Tzu-Chi University , Hualien , Taiwan.
authors.forename: Yao-Wen
authors.initials: YW
authors.lastname: Chang
authors.affiliation: c Institute of Microbiology and Immunology, National Defense Medical Center , Taipei , Taiwan.|d Institute of Preventive Medicine, National Defense Medical Center , Taipei , Taiwan.
authors.forename: Jyh-Hwa
authors.initials: JH
authors.lastname: Kau
authors.affiliation: d Institute of Preventive Medicine, National Defense Medical Center , Taipei , Taiwan.
authors.forename: Hsin-Hsien
authors.initials: HH
authors.lastname: Huang
authors.affiliation: a Department of Molecular Biology and Human Genetics , Tzu-Chi University , Hualien , Taiwan.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Ho
authors.affiliation: a Department of Molecular Biology and Human Genetics , Tzu-Chi University , Hualien , Taiwan.
authors.forename: Yin-Jeh
authors.initials: YJ
authors.lastname: Tzeng
authors.affiliation: a Department of Molecular Biology and Human Genetics , Tzu-Chi University , Hualien , Taiwan.|b Center for Vascular Medicine , Tzu-Chi University , Hualien , Taiwan.
authors.forename: Hsin-Hou
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D000942:Antigens, Bacterial / Q000378:metabolism / Q000633:toxicity*; D001408:Bacillus anthracis / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects; D006487:Hemostasis; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000008:administration & dosage*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; C030325:anthrax toxin
keywords: P-selectin ligand 1; Soluble P-selectin; anthrax lethal toxin; hemostasis; microparticle