A soluble receptor decoy protects rats against anthrax lethal toxin challenge.
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.
Scobie
Heather M
HM
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.
Thomas
Diane
D
Marlett
John M
JM
Destito
Giuseppe
G
Wigelsworth
Darran J
DJ
Collier
R John
RJ
Young
John A T
JA
Manchester
Marianne
M
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
C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008565:Membrane Proteins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors