title: Serum amyloid A protects murine macrophages from lethal toxin-mediated death.
abstract: Lethal toxin, a key virulence factor produced by Bacillus anthracis, induces cell death, in part by disrupting numerous signaling pathways, in mouse macrophages. However, exposure to sublethal doses of lethal toxin allows some cells to survive. Because these pro-survival signaling events occur within a few hours after exposure to sublethal doses, we hypothesized that acute phase proteins might influence macrophage survival. Our data show that serum amyloid A (SAA) is produced in response to lethal toxin treatment. Moreover, pre-treatment of macrophages with exogenous SAA protected macrophages from lethal toxin-mediated death. Exogenous SAA activated the p38 mitogen activated protein kinase (MAP) kinase pathway, while lethal toxin mutants incapable of p38 activation were incapable of causing cell death. Chemical inhibition of the p38 activation pathway abrogated the protective effects of SAA. These data show that SAA affords protection against lethal toxin in mouse macrophages and link this response to the p38 pathway.
authors.affiliation: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Kira
authors.initials: K
authors.lastname: Rose
authors.forename: Paul
authors.initials: P
authors.lastname: Long
authors.forename: Malini
authors.initials: M
authors.lastname: Shankar
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Ballard
authors.forename: Carol F
authors.initials: CF
authors.lastname: Webb
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001408:Bacillus anthracis / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D020011:Protective Agents / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D020011:Protective Agents; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D048051:p38 Mitogen-Activated Protein Kinases
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