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Contribution of Toll-like receptor activation to lung damage after donor brain death.

AbstractINTRODUCTION:
Donor brain death is the first injurious event that can produce inflammatory dysfunction after pulmonary transplantation. This study was designed to determine whether stimulation of the toll-like receptor (TLR) system contributes to the changes produced by brain death.
MATERIALS AND METHODS:
Rats were repeatedly treated with specific agonists for TLR4 or TLR2/6 to desensitize these receptors. Brain death was then induced by inflation of a balloon catheter within the extradural space. Mean arterial pressure changes and inflammatory markers were measured serially by protein and mRNA analysis.
RESULTS:
Both desensitizing pretreatments prevented the neurogenic hypotension (P<0.001) and metabolic acidosis (P<0.001) observed in control animals after brain death. These treatments also reduced the levels of tumor necrosis factor-α and CXCL1 in serum and bronchoalveolar lavage fluid, although desensitization of TLR4 produced a greater inhibition than desensitization of TLR2. Desensitization of TLR4 also reduced (P<0.05) expression of the adhesive integrin CD11b on blood neutrophils after brain death. Examination of mRNA levels in lung tissue 5 hr after brain death showed that desensitization of TLR4 limited the expression of interferon (IFN)-γ, IFNβ, and CXCL10, whereas desensitization of TLR2/6 reduced only the expression of IFNγ.
CONCLUSION:
These results indicate that activation of TLR signaling pathways can contribute to the lung damage produced by brain death; this may increase subsequent graft injury after transplantation.
AuthorsAnthony J Rostron, David M W Cork, Vassilios S Avlonitis, Andrew J Fisher, John H Dark, John A Kirby
JournalTransplantation (Transplantation) Vol. 90 Issue 7 Pg. 732-9 (Oct 15 2010) ISSN: 1534-6080 [Electronic] United States
PMID20671596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD11b Antigen
  • Cell Adhesion Molecules
  • Cytokines
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • RNA
Topics
  • Animals
  • Blood Pressure (drug effects, physiology)
  • Body Weight (drug effects)
  • Brain Death (pathology)
  • CD11b Antigen (genetics)
  • Cell Adhesion Molecules (genetics)
  • Cytokines (metabolism)
  • Flow Cytometry
  • Hemodynamics (drug effects)
  • Lipopolysaccharides (pharmacology)
  • Lung (pathology, physiology)
  • Male
  • Neutrophils (drug effects, physiology)
  • Polymerase Chain Reaction
  • RNA (genetics, isolation & purification)
  • Rats
  • Rats, Wistar
  • Toll-Like Receptor 4 (agonists, physiology)
  • Toll-Like Receptors (physiology)

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