title: Neutralization of B. anthracis toxins during ex vivo phagocytosis.
abstract: Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.
authors.affiliation: Department of Biology, University of Arkansas at Little Rock, 2801 South University Ave., Little Rock, AR 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: April
authors.initials: A
authors.lastname: Jones
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 / Q000737:chemistry / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000737:chemistry; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006001:Glycoconjugates / Q000737:chemistry*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000276:immunology*; D011134:Polysaccharides / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D006001:Glycoconjugates; D011134:Polysaccharides; D011994:Recombinant Proteins; C030325:anthrax toxin; D009569:Nitric Oxide