Abstract | INTRODUCTION: 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.
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Authors | Anthony J Rostron, David M W Cork, Vassilios S Avlonitis, Andrew J Fisher, John H Dark, John A Kirby |
Journal | Transplantation
(Transplantation)
Vol. 90
Issue 7
Pg. 732-9
(Oct 15 2010)
ISSN: 1534-6080 [Electronic] United States |
PMID | 20671596
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD11b Antigen
- Cell Adhesion Molecules
- Cytokines
- Lipopolysaccharides
- Toll-Like Receptor 4
- Toll-Like Receptors
- RNA
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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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