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: Heather M Scobie, Diane Thomas, John M Marlett, Giuseppe Destito, Darran J Wigelsworth, R John Collier, John A T Young, Marianne Manchester
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 192 Issue 6 Pg. 1047-51 (Sep 15 2005) ISSN: 0022-1899 [Print] United States
• PMID: 16107958 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ANTXR2 protein, human
• Antigens, Bacterial
• Bacterial Toxins
• Membrane Proteins
• Receptors, Peptide
• anthrax toxin
• anthrax toxin receptors

Topics

• Animals
• Antigens, Bacterial (metabolism, toxicity)
• Bacterial Toxins (antagonists & inhibitors, metabolism, toxicity)
• CHO Cells
• Cricetinae
• Male
• Membrane Proteins (metabolism, pharmacology)
• Protein Binding
• Rats
• Rats, Inbred F344
• Receptors, Peptide (metabolism)
• Survival Analysis
• Time Factors