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Contribution of Toll-Like Receptor Activation to Lung Damage After Donor Brain Death

Lookup NU author(s): Dr Anthony RostronORCiD, Dr David Cork, Vassillios Avlonitis, Professor Andrew FisherORCiD, Professor John Dark, Emeritus Professor John Kirby


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Introduction. 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-alpha 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)-gamma, IFN beta, and CXCL10, whereas desensitization of TLR2/6 reduced only the expression of IFN gamma. 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.

Publication metadata

Author(s): Rostron AJ, Cork DMW, Avlonitis VS, Fisher AJ, Dark JH, Kirby JA

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2010

Volume: 90

Issue: 7

Pages: 732-739

Print publication date: 01/10/2010

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins


DOI: 10.1097/TP.0b013e3181eefe02


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Funder referenceFunder name
British Transplantation Society
0768830The Wellcome Trust