title: p53-dependent and -independent pathways of apoptotic cell death in sepsis.
abstract: Sepsis induces extensive apoptosis of lymphocytes, which may be responsible for the profound immune suppression of the disorder. Two potential pathways of sepsis-induced lymphocyte apoptosis, Fas and p53, were investigated. Lymphocyte apoptosis was evaluated 20-22 h after sepsis by annexin V or DNA nick-end labeling. Fas receptor-deficient mice had no protection against sepsis-induced apoptosis in thymocytes or splenocytes. p53 knockout mice (p53-/-) had complete protection against thymocyte apoptosis but, surprisingly, had no protection in splenocytes. p53-/- mice had no improvement in sepsis survival compared with appropriately matched control mice with sepsis. We conclude that both p53-dependent and p53-independent pathways of cell death exist in sepsis. This differential apoptotic response of thymocytes vs splenocytes in p53-/- mice suggests that either the cellular response or the death-inducing signal is cell-type specific in sepsis. The fact that p53-/- lymphocytes of an identical subtype (CD8-CD4+) were protected in thymi but not in spleens indicates that cell susceptibility to apoptosis differs depending upon other unidentified factors.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA. hotch@morpheus.wustl.edu
authors.forename: R S
authors.initials: RS
authors.lastname: Hotchkiss
authors.forename: K W
authors.initials: KW
authors.lastname: Tinsley
authors.forename: J J
authors.initials: JJ
authors.lastname: Hui
authors.forename: K C
authors.initials: KC
authors.lastname: Chang
authors.forename: P E
authors.initials: PE
authors.lastname: Swanson
authors.forename: A M
authors.initials: AM
authors.lastname: Drewry
authors.forename: T G
authors.initials: TG
authors.lastname: Buchman
authors.forename: I E
authors.initials: IE
authors.lastname: Karl
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019014:fas Receptor / Q000235:genetics
chemical_list: D017304:Annexin A5; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor