Antibodies against anthrax protective antigen promote macrophage death.

2004 AUG 11 - (NewsRx.com & NewsRx.net) -- A subset of monoclonal antibodies against anthrax protective antigen increases lethal toxin-mediated killing of murine macrophages.

"We investigated the ability of using monoclonal antibodies (MAbs) against anthrax protective antigen (PA), an anthrax exotoxin component, to modulate exotoxin cytotoxic activity on target macrophage cell lines. Anthrax PA plays a critical role in the pathogenesis of Bacillus anthracis infection. PA is the cell-binding component of the two anthrax exotoxins: lethal toxin (LeTx) and edema toxin. Several MAbs that bind the PA component of LeTx are known to neutralize LeTx-mediated killing of target macrophages," scientists writing in the journal Infection and Immunity report.

"Here we describe for the first time an overlooked population of anti-PA MAbs that, in contrast, function to increase the potency of LeTx against murine macrophage cell lines," said Nehal Mohamed and collaborators at Elusys Therapeutics, Inc. and the U.S. Army Medical Research Institute of Infectious Diseases. "The results support a possible mechanism of enhancement: binding of MAb to PA on the macrophage cell surface stabilizes the PA by interaction of MAb with macrophage Fcgamma receptors. This results in an increase in the amount of PA bound to the cell surface, which in turn leads to an enhancement in cell killing, most likely due to ...