Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis. Proc Natl Acad Sci U S A 2003 May 27;100(11):6724-9
Date
05/09/2003Pubmed ID
12736377Pubmed Central ID
PMC164514DOI
10.1073/pnas.1031788100Scopus ID
2-s2.0-0038312126 (requires institutional sign-in at Scopus site) 160 CitationsAbstract
In sepsis, both necrotic and apoptotic cell death can occur. Apoptotic cells induce anergy that could impair the host response, whereas necrotic cells cause immune activation that might result in enhanced antimicrobial defenses. We determined whether adoptive transfer of apoptotic or necrotic cells impacted survival in a clinically relevant sepsis model. We also evaluated the effects of adoptive transfer of apoptotic or necrotic cells on the prototypical TH1 and TH2 cytokines IFN-gamma and IL-4, respectively. C57BL6/J mice had adoptive transfer of apoptotic (irradiated) or necrotic (freeze thaw) splenocytes. Controls received saline. Apoptotic cells greatly increased mortality, whereas necrotic splenocytes markedly improved survival, P < or = 0.05. The contrasting effects that apoptotic or necrotic cells exerted on survival were mirrored by opposite effects on splenocyte IFN-gamma production with greatly decreased and increased production, respectively. Importantly, either administration of anti-IFN-gamma antibodies or use of IFN-gamma knockout mice prevented the survival benefit occurring with necrotic cells. This study demonstrates that the type of cell death impacts survival in a clinically relevant model and identifies a mechanism for the immune suppression that is a hallmark of sepsis. Necrotic cells (and likely apoptotic cells) exert their effects via modulation of IFN-gamma
Author List
Hotchkiss RS, Chang KC, Grayson MH, Tinsley KW, Dunne BS, Davis CG, Osborne DF, Karl IEMESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
Antibodies
Apoptosis
Colony Count, Microbial
Flow Cytometry
Histocompatibility Antigens Class II
Interferon-gamma
Mice
Mice, Inbred C57BL
Necrosis
Sepsis
Spleen
Survival Rate
