title: Role of chondroitin sulfate C in the action of anthrax toxin.
abstract: Anthrax toxin is produced by Bacillus anthracis, the causative agent of anthrax, and is responsible for the majority of disease symptoms. The toxin consists of 3 proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF), which combine to form lethal and edema toxin. Glycosaminoglycans, which are present on the surface of cells, were investigated with regard to their role in toxicity resulting from anthrax toxin exposure. Lethal toxin-induced cytotoxicity of the RAW 264.7 cells was significantly inhibited by the addition of chondroitin sulfate C as determined by the MTT assay. By contrast, several other glycosaminoglycans, including heparin, heparan sulfate, and dermatan sulfate did not show significant levels of inhibition. Studies utilizing fluorescence-labeled PA demonstrated decreased PA binding to RAW 264.7 cells with the addition of chondroitin sulfate C. Formation of PA oligomers at the surface of cells after binding was also inhibited by chondroitin sulfate C. Interestingly, enzymatic degradation of endogenous chondroitin sulfate C from the cell surface with chondroitinase ABC was accompanied by increased sensitivity to the toxin. These findings were further confirmed by pretreating cells with sodium chlorate to reduce the degree of cell surface glycosaminoglycans sulfation. In addition, chondroitin sulfate C effectively inhibits edema toxin-induced cAMP accumulation in cells. Our results indicate that chondroitin sulfate C may play an important role in the toxicity of anthrax toxin.
authors.affiliation: Department of Life Science, Sogang University, Shinsu-Dong, Mapo, Seoul 121-742, Republic of Korea.
authors.forename: Hyun Chan
authors.initials: HC
authors.lastname: Ahn
authors.forename: Na Young
authors.initials: NY
authors.lastname: Kim
authors.forename: Gyeung Haeng
authors.initials: GH
authors.lastname: Hur
authors.forename: Jai Myung
authors.initials: JM
authors.lastname: Yang
authors.forename: Sungho
authors.initials: S
authors.lastname: Shin
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002809:Chondroitin Sulfates / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D002809:Chondroitin Sulfates