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Blood. 2009 Mar 19;113(12):2742-5. doi: 10.1182/blood-2008-09-178038. Epub 2009 Jan 23.

Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and improves survival.

Author information

1
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. Lamkanfi.Mohamed@gene.com

Abstract

Extensive apoptosis of leukocytes during sepsis and endotoxic shock constitutes an important mechanism linked to the excessive mortality associated with these disorders. Caspase inhibitors confer protection from endotoxin-induced lymphocyte apoptosis and improve survival, but it is not clear which caspases mediate lipopolysaccharide (LPS)-induced lymphocyte apoptosis and mortality. We report here that the apoptotic executioner caspase-7 was activated in the splenocytes of LPS-injected mice, suggesting a role for caspase-7 in lymphocyte apoptosis. Indeed, caspase-7-deficient mice were resistant to LPS-induced lymphocyte apoptosis and were markedly protected from LPS-induced lethality independently of the excessive production of serum cytokines. These results reveal for the first time a nonredundant role for caspase-7 in vivo and identify caspase-7 inhibition as a component of the mechanism by which caspase inhibitors protect from endotoxin-induced mortality.

PMID:
19168786
PMCID:
PMC2661861
DOI:
10.1182/blood-2008-09-178038
[Indexed for MEDLINE]
Free PMC Article

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