title: Glycoconjugates prevent B. anthracis toxin-induced cell death through binding while activating macrophages.
abstract: Bacillus anthracis toxins may be attenuated if macrophages could neutralize toxins upon contact or exposure. Glycoconjugate-bearing polymers, which have been shown to bind to Bacillus spores, were tested for recognition and binding of protective antigen (PA), lethal factor (LF), and edema factor (EF) toxins. We have demonstrated modulation of macrophage activity following exposure to these toxins. Without glycoconjugate (GC) activation, murine macrophages were killed by Bacillus toxins. GCs were shown to have a protective influence, sparing macrophages from toxin-induced cell death, as shown by increased macrophage cell viability based on trypan blue assay. Increased levels of inducible nitric oxide (NO) production by macrophages in presence of GCs suggest that GCs provide an activation signal for macrophages and stimulate their function. Results hint to GCs that promote neutralization of Bacillus toxins, block toxin-induced macrophage death, while increasing macrophage activation. Polymeric GCs may suggest novel approaches to improve existing or develop new vaccines as well as immunotherapeutics.
authors.affiliation: Department of Biology, University of Arkansas at Little Rock, 72204, USA. omtarasenko@ualr.edu
authors.forename: Olga
authors.initials: O
authors.lastname: Tarasenko
authors.forename: Ashley
authors.initials: A
authors.lastname: Scott
authors.forename: Lee
authors.initials: L
authors.lastname: Soderberg
authors.forename: Pierre
authors.initials: P
authors.lastname: Alusta
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001408:Bacillus anthracis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D006001:Glycoconjugates / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D006001:Glycoconjugates; D011108:Polymers; C030325:anthrax toxin; D009569:Nitric Oxide