Altered immunoreactivity of HPC-1/syntaxin 1A in proliferated nerve fibersin the human aganglionic colon of Hirschsprung's disease

To clarify the pathogenesis of excessive proliferation of extrinsic nerve f ibers in the aganglionic colon of patients with Hirschsprung's disease (HD) , we immunohistochemically determined the role that exocytosis-related prot eins play in the regulation of exocytosis using the antibody to HPC-1/synta xin1A, an exocytosis-related protein. Localization of exocytosis-related pr oteins (HPC-1/syntaxin1A, N-ethylmalemide-sensitive fusion protein (NSF), s oluble NSF attachment protein (SNAP), synaptotagmin, synaptobrevin, and syn aptosome-associated protein 25 (SNAP-25)) was determined in surgical specim ens obtained from normal proximal and aganglionic distal segments of the co lon of 7 infant patients with HD. In the normal ganglionic colon, Auerbach' s plexus, Meisner's plexus, nerve fibers in the muscle layer, and ganglion cells were immunopositive for all six kinds of antisera. In the aganglionic segments, numerous proliferated nerve fibers and hypertrophied nerve bundl es were detected in the submucosal layer and myenteric layer by NSF, SNAP, synaptotagmin, synaptobrevin, and SNAP-25. However, HPC-1/syntaxin 1A was n ot recognized in the proliferated nerve fibers of the submucosal layer or t he hypertrophied nerve bundles of the aganglionic segment. These findings s how that immunoreactivity of HPC-1/syntaxin 1A was decreased in the affecte d bowel segments of patients with HD and may be related to the pathogenesis of extrinsic nerve-fiber proliferation in the aganglionic colon of HD.