Impaired expression of neural cell adhesion molecule L1 in the extrinsic nerve fibers in Hirschsprung's disease

Abstract

Immunohistochemical studies on the ganglionic and aganglionic segment in Hirschsprung's disease (HD) were carried out using antibodies against three neural membrane proteins, Thy-1, Integrin α5, and L1. Enteric neural elements were immunostained with antibodies against neurofilament, which is the neuronal cytoskeletal protein. In ganglionic segments, neurofilament-immunoreactivity was detected in neuronal cell bodies and fine nerve fibers of the myenteric and submucosal plexuses. All of these neural elements were immunopositive for Thy-1, integrin α5, and L1. In aganglionic segments, no intrinsic neurons were detected, and instead, hypertrophied nerve bundles were observed in intermuscular space, in submucosa, and in circular muscle layer by immunochemistry for neurofilament. These hypertrophied nerve bundles were immunopositive with anti-Thy-1 and anti-integrin α5 antibodies. However, they were not immunostained with anti-L1 in all five cases. These findings indicate that the expression of L1 molecule, which plays an important role in cell adhesion, neural cell migration, and neurite outgrowth, is impaired in the extrinsic nerve fibers in aganglionic colon. And this may perturb neural creast migration and adequate neurite outgrowth, with resulting aganglionic segment and abnormal nerve bundles of extrinsic fibers in HD.