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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2742-2745. Prepublished online as a Blood First Edition Paper on January 23, 2009; DOI 10.1182/blood-2008-09-178038. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-09-178038v1 113/12/2742    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lamkanfi, M. Articles by Kanneganti, T.-D. Search for Related Content PubMed PubMed Citation Articles by Lamkanfi, M. Articles by Kanneganti, T.-D. Related Collections Immunobiology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief Report Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and improves survival Mohamed Lamkanfi1, Lilian O. Moreira1,2, Patrudu Makena1, Diana C. J. Spierings1, Kelli Boyd3, Peter J. Murray1,2, Douglas R. Green1, and Thirumala-Devi Kanneganti1 Departments of 1 Immunology, and 2 Infectious Diseases, and 3 ARC Diagnostic Laboratory, St Jude Children's Research Hospital, Memphis, TN 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Sharma, Q. Li, B. B. Mishra, M. J. Georges, and J. M. Teale Vaccination with an Attenuated Strain of Francisella novicida Prevents T-Cell Depletion and Protects Mice Infected with the Wild-Type Strain from Severe Sepsis Infect. Immun., October 1, 2009; 77(10): 4314 - 4326. [Abstract] [Full Text] [PDF] M. Lamkanfi, R. K. S. Malireddi, and T.-D. Kanneganti Fungal Zymosan and Mannan Activate the Cryopyrin Inflammasome J. Biol. Chem., July 31, 2009; 284(31): 20574 - 20581. [Abstract] [Full Text] [PDF]

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