Rôle des eicosanoïdes post-greffe :
implication dans la bronchiolite oblitérante
Chronic rejection occurs, in the lung, in the form of bronchiolitis obliterans (BO), an inflammatory and fibroproliferative disease that leads to the obliteration of the bronchioles. A concept of the pathogenesis of BO has been suggested and several risk factors are associated to it, however, the exact etiology of this disease remains unknown. Studies have suggested that an imbalance of leukotrienes (LT) over prostaglandins (PG) promotes pulmonary fibrosis. The levels of LT and PG in the human lung post-transplantation are unknown. We propose that an imbalance of cysteinyl leukotrienes (CysLT) on PGE2 exists in the transplanted lung and may be implicated in the pathogenesis of BO. We also suggest that leukotrienes contribute to fibrosis through epithelial-mesenchymal transition (EMT). In order to test these hypotheses, we have determined the levels of CysLTs and PGE2 in human transplanted lung bronchoalveolar lavage fluid (BALf) samples and their clinical correlations. We have also determined the capacity of CysLT to induce the expression of EMT markers in vitro. We found high average levels of CysLT and PGE2 in the BAL of transplant patients. A predominant peak of CysLT over PGE2 was observed at 52 weeks post-transplantation and two risk factors for BO, CMV infections and Aspergillus were associated with CysLT/PGE2 ratio> 1. According to our experimental parameters, CysLT can induce the repression of epithelial markers but do not induce the expression of mesenchymal markers in vitro in small airway epithelial cells.
Cysteinyl leukotrienes Prostaglandins Lung transplantation Chronic rejection Epithelial-mesenchymal transition