BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation.
J Exp Med
; 202(1): 97-110, 2005 Jul 04.
Article
em En
| MEDLINE
| ID: mdl-15998790
ABSTRACT
Leukotriene B4 is a lipid mediator that recently has been shown to have potent chemotactic activity for effector T lymphocytes mediated through its receptor, BLT1. Here, we developed a novel murine model of acute lung rejection to demonstrate that BLT1 controls effector CD8+ T cell trafficking into the lung and that disruption of BLT1 signaling in CD8+ T cells reduces lung inflammation and mortality in the model. In addition, we used BLT1-deficient mice and a BLT1 antagonist in two tracheal transplant models of lung transplantation to demonstrate the importance of BLT1 for the recruitment of T cells into tracheal allografts. We also show that BLT1-mediated CD8+ T cell recruitment plays an important role in the development of airway fibroproliferation and obliteration. Finally, in human studies of lung transplant recipients, we found that BLT1 is up-regulated on T lymphocytes isolated from the airways of patients with obliterative bronchiolitis. These data demonstrate that BLT1 contributes to the development of lung rejection and obliterative bronchiolitis by mediating effector T lymphocyte trafficking into the lung. This is the first report that describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease and identifies BLT1 as a potential therapeutic target after lung transplantation.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Bronquiolite Obliterante
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Transplante de Pulmão
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Receptores do Leucotrieno B4
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Linfócitos T CD8-Positivos
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Rejeição de Enxerto
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article