Document Detail


Modulation of the Bcl-2 family blocks sepsis-induced depletion of dendritic cells and macrophages.
MedLine Citation:
PMID:  18838943     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study examined the fate of dendritic cells (DCs) and macrophages (M Phi) in vivo in a murine model of sepsis. Wild-type, knockout, and transgenic mice were used to examine the role of Bcl-2 family members on the regulation of splenic DCs and M Phi survival. Bim knockout (Bim) mice and mice overexpressing Bcl-2 in selected hematopoietic cells were used: (a) overexpression of Bcl-2 in all hematopoietic cells using a vav promoter (Vav-Bcl-2) and (b) overexpression of Bcl-2 in all Major histocompatibility complex (MHC) class I cells (H-2K-Bcl-2). Mice underwent sham surgery or cecal ligation and puncture, and absolute numbers of splenic DCs and M Phi were determined. Importantly, two distinct M Phi populations, that is, well-differentiated "mature" M Phi population and a less differentiated "immature," "monocyte-like" (IM Phi) population were identified that demonstrated differential susceptibility to apoptosis. In wild-type mice, sepsis induced a 64% +/- 7% and a 77% +/- 3% decrease in absolute cell numbers of splenic DCs and IM Phi, respectively (n = 7, P < 0.05). Mature M Phi were not depleted in sepsis. No significant cell depletion was evident in Vav-Bcl-2, H-2K-Bcl-2, or Bim mice. We conclude that sepsis induces a major depletion of developing M Phi as well as DCs, and this depletion may be an important mechanism of immune suppression in sepsis.
Authors:
Octavia M Peck-Palmer; Jacqueline Unsinger; Katherine C Chang; Jacquelyn S McDonough; Harris Perlman; Jonathan E McDunn; Richard S Hotchkiss
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  31     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-18     Completed Date:  2009-05-20     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  359-66     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dendritic Cells / immunology*,  pathology
Flow Cytometry
Gene Expression Regulation
Lymphocyte Depletion
Macrophages / immunology*,  pathology
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-bcl-2 / genetics,  physiology*
Sepsis / immunology*,  pathology
Spleen / immunology,  pathology
Grant Support
ID/Acronym/Agency:
GM055194/GM/NIGMS NIH HHS; GM055194-10S1/GM/NIGMS NIH HHS; GM44118/GM/NIGMS NIH HHS; P30 CA91842/CA/NCI NIH HHS; R01 GM044118/GM/NIGMS NIH HHS; R01 GM044118-08/GM/NIGMS NIH HHS; R01 GM055194/GM/NIGMS NIH HHS; R01 GM055194-05/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2
Comments/Corrections

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