Differential expression of Neuropeptide Y (NPY) and NPY receptors 1/2 between rat lung and kidney allografts

Abstract

Recently, our group described a strong leukocytic expression of NPY in the rat. During acute renal graft rejection, we observed a drastical down-regulation of NPY by mononuclear leukocytes accumulating in blood vessels of rat kidneys. Concurrently, the expression of NPY receptors Y1 and Y2 was increased. NPY, a sympathetic co-mediator modulating immune functions, may regulate leukocyte accumulation in graft blood vessels. Lung transplantation is the therapeutic measure of last resort for patients with end-stage lung disease. Compared to kidney transplants, the long-term outcomes of lung grafts are worse. This study addresses the expression of NPY and its receptors in acute rejection of pulmonary grafts. Orthotopic left lung transplantations were performed in the Dark Agouti to Lewis rat strain combination. Animals were sacrificed 4 days after surgery, one day before irreversible graft destruction. Time-matched isografts and untreated organs served as controls. The expression of NPY and its receptors was analyzed by quantitative RT-PCR, Western Blotting, radioimmunoassay and/or immunohistochemistry. Surprisingly, in lung allografts, mononuclear intravascular leukocytes, obtained by vascular perfusion, and intraalveolar leukocytes from bronchoalveolar lavages, abundantly expressed NPY mRNA during acute rejection. In intraalveolar leukocytes, but not in leukocytes isolated from the blood vessels of allografts, we observed an increase in Y1 expression. NPY peptide concentrations in the lung lavage fluids were higher in transplanted allografts compared to control lungs. Our study verifies distinctive organ-specific features of the mononuclear leukocytes in lung allografts. The observed differences between lungs and kidneys may be responsible for the moderate number of leukocytes accumulating in pulmonary graft vessels compared to the massive number in renal grafts. The mechanisms involved in the regulations of the NPY/NPY receptor system are currently under investigation.