Document Detail

Early trauma-hemorrhage-induced splenic and thymic apoptosis is gut-mediated and toll-like receptor 4-dependent.
MedLine Citation:
PMID:  23542401     Owner:  NLM     Status:  MEDLINE    
Immune depression after trauma-hemorrhage has been implicated as an important factor in the pathogenesis of sepsis and septic-organ failure. Although recent studies have implicated immune-cell apoptosis as an important factor in the evolution of this posttrauma immune-suppressed state, neither the initial triggers that induce this response nor the cellular pathways through which these triggering pathways act have been fully defined. Thus, the current study tests the hypothesis that acute splenic and thymic immune-cell apoptosis developing after trauma-hemorrhagic shock (T/HS) is due to gut-derived factors carried in intestinal lymph and that this T/HS lymph-induced immune depressed state is mediated through Toll-like receptor 4 (TLR4). The first set of experiments documented that T/HS caused both thymic and splenic immune-cell apoptosis as measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase-3 immunohistochemistry and that this increase in apoptosis was totally abrogated by mesenteric lymph duct ligation. In subsequent experiments, mesenteric lymph collected from animals subjected to T/HS or trauma-sham shock were injected into TLR4-deficient (TLR4mut) mice or their wild-type (WT) littermates. Trauma-hemorrhagic shock, but not trauma-sham shock, lymph caused splenic apoptosis in the WT mice. However, the TLR4mut mice were resistant to T/HS lymph-induced splenic apoptosis. Furthermore, the WT, but not the TLR4mut mice developed splenic apoptosis after actual T/HS. In conclusion, gut-derived factors appear to initiate a sequence of events that leads to an acute increase in splenic and thymic immune-cell apoptosis, and this process is TLR4-dependent.
Gregory Tiesi; Diego Reino; Leonard Mason; David Palange; Jacquelyn N Tomaio; Edwin A Deitch
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  39     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-17     Completed Date:  2013-12-30     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  507-13     Citation Subset:  IM    
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MeSH Terms
Apoptosis / immunology
Immune Tolerance
Intestines / immunology*
Lymph / immunology
Mice, Inbred C3H
Mice, Mutant Strains
Rats, Sprague-Dawley
Shock, Hemorrhagic / immunology*,  pathology
Shock, Traumatic / immunology*,  pathology
Spleen / immunology*,  pathology
Sus scrofa
Thymus Gland / immunology*,  pathology
Toll-Like Receptor 4 / immunology
Grant Support
Reg. No./Substance:
0/Tlr4 protein, rat; 0/Toll-Like Receptor 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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