epidermal-growth-factor and Bronchiolitis-Obliterans

The main cause of morbidity and mortality after lung transplantation (LT) is bronchiolitis obliterans syndrome (BOS). Anti-HLA antibodies development after LT has been shown to play an important role in BOS pathogenesis. However, the nature of non-HLA antibodies developed after LT and their role in BOS pathogenesis have not been determined.. Sera from 16 BOS+ patients and 11 BOS- patients were collected at 12, 24, 36, and 48 months after LT. Anti-HLA class I and class II antibodies were absorbed with pooled human platelets and pooled human lymphoblastoid cell lines, respectively. Then, the presence of non-HLA antibodies against several cell lines from different origin was determined by flow cytometric analysis. Antibody-positive samples were tested for induction of proliferation and growth factor production in two selected airway epithelial cell (AEC) lines.. Five of 16 BOS+ patients (31.2%) and 0 of 11 BOS- patients (0%) developed anti-AEC antibodies after LT (P=0.05). No reactivity against endothelial cells, lymphocytes, monocytes, or granulocytes was detected. Further analysis of two selected sera demonstrated the development of reactivity against a 60-kDa antigen expressed by 60% of AEC lines and only 12% of cell lines from other tissues. Antibody binding to this antigen induced intracellular Ca++ influx, tyrosine phosphorylation, proliferation, and up-regulation of transforming growth factor-beta and heparin-binding epidermal growth factor mRNA transcription in AECs.. These results indicate that anti-AEC antibodies may play a role in the immunopathogenesis of BOS in the absence of anti-HLA antibodies.

Topics: Antibodies; Bronchiolitis Obliterans; Cell Division; Cell Line; Epidermal Growth Factor; Epithelial Cells; Heparin-binding EGF-like Growth Factor; HLA Antigens; Humans; Intercellular Signaling Peptides and Proteins; Lung; Lung Transplantation; Phosphorylation; Postoperative Period; Transforming Growth Factor beta; Tyrosine; Up-Regulation