| Modulation of the Bcl-2 family blocks sepsis-induced depletion of dendritic cells and macrophages. | |
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MedLine Citation:
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PMID: 18838943 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 31 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-18 Completed Date: 2009-05-20 Revised Date: 2013-04-23 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 359-66 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Proto-Oncogene Proteins c-bcl-2 |
| Comments/Corrections | |
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