Increased alveolar macrophage nuclear factor-kappa B activation and macrophage inhibitory protein-1 alpha levels in lung transplant patients

Background. Lung transplantation is increasingly used as the treatment for many end-stage pulmonary diseases. A major cause of morbidity and mortality in patients who undergo lung transplantation is rejection of the allograft , Proinflammatory macrophage-derived cytokines may sustain and/or enhance t he immunological response to lung allograft antigens. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that regulates the production of man y of these cytokines and growth factors in alveolar macrophages (AMs). The aim of our study was to evaluate the activation of NF-kappaB in AMs and the levels of one of the proinflammatory cytokines whose production it control s, macrophage inhibitory protein-1 alpha (MIP-1 alpha), in AMs from transpl anted lungs compared to those from healthy controls. Methods. Twenty-eight (28) transplant recipients were included in the study . NF kappaB activation was evaluated by electrophoretic mobility shift assa y of whole cell extracts and by immunohistochemical analysis on cytospin pr eparations. Concentrated bronchoalveolar lavage fluid was analyzed by enzym e-linked immunosorbent assay for MIP-1 alpha levels. Results. NF-kappaB was activated in alveolar macrophages from transplant pa tients as compared to healthy controls. MIP-1 alpha levels in epithelial-li ning fluid were elevated in transplant patients as compared to healthy cont rols. Increased MIP-1 alpha levels correlated with viral infections in the transplant patients. Neither finding was found to correlate with acute reje ction by transbronchial biopsy. Conclusions. These results demonstrate that NF-kappaB activation and MIP-1 alpha levels are increased in transplanted lungs and may play a role in the inflammatory cytokine cascade that leads to the long-term tissue damage an d allograft rejection in these patients.