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: R S Hotchkiss, K W Tinsley, J J Hui, K C Chang, P E Swanson, A M Drewry, T G Buchman, I E Karl
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 7 Pg. 3675-80 (Apr 01 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10725725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Annexin A5
• Tumor Suppressor Protein p53
• fas Receptor

Topics

• Animals
• Annexin A5 (metabolism)
• Apoptosis (genetics, immunology)
• Disease Models, Animal
• Flow Cytometry
• Immunophenotyping
• Mice
• Mice, Inbred C57BL
• Mice, Inbred MRL lpr
• Mice, Knockout
• Mice, Mutant Strains
• Peritonitis (genetics, immunology, mortality, pathology)
• Sepsis (genetics, immunology, mortality, pathology)
• Signal Transduction (genetics, immunology)
• Survival Analysis
• Tumor Suppressor Protein p53 (deficiency, genetics, physiology)
• fas Receptor (genetics)