title: A soluble receptor decoy protects rats against anthrax lethal toxin challenge.
abstract: Successful postexposure treatment for inhalation anthrax is thought to include neutralization of anthrax toxin. The soluble anthrax toxin receptor/tumor endothelial marker 8 and capillary morphogenesis protein 2 (sATR/TEM8 and sCMG2, respectively) receptor decoys bind to anthrax toxin protective antigen (PA) and compete with cellular receptors for binding. Here, we show that, in a tissue-culture model of intoxication, sCMG2 is a 11.4-fold more potent antitoxin than sATR/TEM8 and that this increased activity corresponds to an approximately 1000-fold higher PA-binding affinity. Stoichiometric concentrations of sCMG2 protect rats against lethal toxin challenge, making sCMG2 one of the most effective anthrax antitoxins described to date.
authors.affiliation: Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Scobie
authors.forename: Diane
authors.initials: D
authors.lastname: Thomas
authors.forename: John M
authors.initials: JM
authors.lastname: Marlett
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Destito
authors.forename: Darran J
authors.initials: DJ
authors.lastname: Wigelsworth
authors.forename: R John
authors.initials: RJ
authors.lastname: Collier
authors.forename: John A T
authors.initials: JA
authors.lastname: Young
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism* / Q000633:toxicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000633:toxicity; D016466:CHO Cells; D006224:Cricetinae; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D018000:Receptors, Peptide / Q000378:metabolism*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008565:Membrane Proteins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors