Increased alveolar macrophage nuclear factor-kappa B activation and macrophage inhibitory protein-1alpha 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 the immunological response to lung allograft antigens. Nuclear factor-kappa B (NF-kappaB) is a transcription factor that regulates the production of many 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 controls, macrophage inhibitory protein-1alpha (MIP-1alpha), in AMs from transplanted lungs compared to those from healthy controls.


METHODS
Twenty-eight (28) transplant recipients were included in the study. NFkappaB activation was evaluated by electrophoretic mobility shift assay of whole cell extracts and by immunohistochemical analysis on cytospin preparations. Concentrated bronchoalveolar lavage fluid was analyzed by enzyme-linked immunosorbent assay for MIP-1alpha levels.


RESULTS
NF-kappaB was activated in alveolar macrophages from transplant patients as compared to healthy controls. MIP-1alpha levels in epithelial-lining fluid were elevated in transplant patients as compared to healthy controls. Increased MIP-1alpha levels correlated with viral infections in the transplant patients. Neither finding was found to correlate with acute rejection by transbronchial biopsy.


CONCLUSIONS
These results demonstrate that NF-kappaB activation and MIP-1alpha levels are increased in transplanted lungs and may play a role in the inflammatory cytokine cascade that leads to the long-term tissue damage and allograft rejection in these patients.
Farver
C F
CF
Department of Anatomic Pathology, Transplantation Center, The Cleveland Clinic Foundation, OH 44195-5038, USA.
Raychaudhuri
B
B
Malur
A
A
Drazba
J
J
Maurer
J
J
Tubbs
R
R
Mehta
A C
AC
Schilz
R
R
Thomassen
M J
MJ
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016040:Lung Transplantation / Q000473:pathology*; D008262:Macrophage Activation; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D016328:NF-kappa B / Q000502:physiology*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B