Persistence of Intrinsic Neurones and Possible Phenotypic Changes after Extrinsic Denervation of Human Respiratory Tract by Heart-Lung Transplantation

Abstract

Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.

Mucosal Nerves in Endobronchial Biopsies in Asthma and Non-Asthma

“…The antisera used to detect SP and CGRP have both previously been substantiated in other tissue, be ing used to delineate neuropeptide-containing nerves in the central nervous system [ 16], skin [ 17] and respir atory tract [18]. Within resected lung tissue, SP-im munoreactive nerves are difficult to detect or absent, a finding consistent with the reported findings of Ol lerenshaw et al [11,12] in non-asthmatic subjects.…”

Initial increase and subsequent loss of vasoactive intestinal polypeptide immunoreactivity in acetylcholinesterase-positive neurons of mouse islets transplanted to the kidney

“…The cause of this decline is unclear. Although not observed in all transplantation studies (Adeghate and Donath 1990; Korsgren et al 1992Korsgren et al , 1993Portis et al 1994;Shen et al 1993;Springall et al 1990), a similar decrease in the density of VIP-LI nerve fibers was also reported in rat ovaries autotransplanted to the neck (Lara et al 1992) and rat smooth muscle cells grafted to the anterior chamber of the eye (Hiebert and Smith 1994). It should be noted, however, that the AChE-positive innervation was not down-regulated in the present islet grafts.…”

Peptide-Containing Nerve Fibers in Human Airways: Distribution and Coexistence Pattern

“…In human airways, VIP-containing nerve fibers are dis tributed predominantly in tracheobronchial smooth mus cle, around blood vessels and seromucous glands and in nerve cell bodies of local ganglia [2,7,[27][28][29], NPY-containing fibers in human airways are localized mainly around blood vessels and within glands [2,11]. A few NPYcontaining nerve cell bodies have been demonstrated in local ganglia [2], SP-immunoreactive nerve fibers have been reported to be sparsely distributed in association with the epithelium, around blood vessels and glands and as single fibers within human airway smooth muscle [2,3,[30][31][32][33].…”