Impaired expression of neural cell adhesion molecule L1 in the extrinsic nerve fibers in Hirschsprung's disease.
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 alpha5, 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 alpha5, 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 alpha5 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 crest migration and adequate neurite outgrowth, with resulting aganglionic segment and abnormal nerve bundles of extrinsic fibers in HD.
Ikawa
H
H
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kawano
H
H
Takeda
Y
Y
Masuyama
H
H
Watanabe
K
K
Endo
M
M
Yokoyama
J
J
Kitajima
M
M
Uyemura
K
K
Kawamura
K
K
D015703:Antigens, CD / Q000032:analysis; D003106:Colon / Q000737:chemistry / Q000294:innervation*; D017615:Enteric Nervous System / Q000737:chemistry; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D007223:Infant; D039482:Integrin alpha5; D016023:Integrins / Q000032:analysis; D039841:Leukocyte L1 Antigen Complex; D009412:Nerve Fibers / Q000737:chemistry* / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000032:analysis*; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D018800:Thy-1 Antigens / Q000032:analysis
D015703:Antigens, CD; D039482:Integrin alpha5; D016023:Integrins; D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D016900:Neurofilament Proteins; D018800:Thy-1 Antigens