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Am. J. Respir. Cell Mol. Biol., Volume 20, Number 6, June, 1999 1268-1273

Calcitonin Gene-Related Peptide-Immunoreactive Nerves and Neuroendocrine Cells after Lung Transplantation in the Rat

Annick Buvry, Yu-Ru Yang, Reza Tavakoli, and Nelly Frossard

INSERM U425, Faculté de Pharmacie, Illkirch; Laboratoire de Physiologie, UFR de Bobigny, Bobigny, France; and Heart Center, Klinik im Schachen, Aarau, Switzerland

Bronchial innervation is interrupted at lung transplantation. Nerve fibers with cell bodies above the section, such as sensory C fibers, should degenerate. Using histofluorescence, we evaluated calcitonin gene-related peptide (CGRP) immunoreactivity in syngeneic Lewis rats 1 and 5 mo after unilateral lung transplantation and in controls. CGRP-immunoreactive (IR) neuroendocrine cells were located within the epithelium of large and small bronchi. At 1 mo after transplantation, their number had significantly increased in large bronchi and had normalized 5 mo after transplantation. The density of CGRP-IR fibers in control lungs gradually decreased from large (0.35 ± 0.02 µm/µm basal lamina) to small (0.23 ± 0.02) and peripheral bronchi (0.12 ± 0.01). At 1 mo after lung transplantation, few CGRP-IR fibers were observed in large bronchi (0.17 ± 0.02), fewer in small bronchi (0.04 ± 0.01) (P < 0.01), and none in peripheral bronchi. At 5 mo after lung transplantation, transplanted lungs still had fewer CGRP-IR fibers in large (0.22 ± 0.02) and small (0.11 ± 0.02) bronchi (P < 0.02) than did controls, but there were, nonetheless, more in the small bronchi than at 1 mo after transplantation (P < 0.01). Additionally, few CGRP fibers were present in the peripheral bronchi (0.03 ± 0.01) (P < 0.01). These results clearly demonstrate the occurrence of denervation followed by partial reinnervation with CGRP-IR fibers after transplantation in rat lung.




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