Altered immunoreactivity of HPC-1/syntaxin 1A in proliferated nerve fibers in the human aganglionic colon of Hirschsprung's disease.
To clarify the pathogenesis of excessive proliferation of extrinsic nerve fibers in the aganglionic colon of patients with Hirschsprung's disease (HD), we immunohistochemically determined the role that exocytosis-related proteins play in the regulation of exocytosis using the antibody to HPC-1/syntaxin 1A, an exocytosis-related protein. Localization of exocytosis-related proteins (HPC-1/syntaxin 1A, N-ethylmalemide-sensitive fusion protein (NSF), soluble NSF attachment protein (SNAP), synaptotagmin, synaptobrevin, and synaptosome-associated protein 25 (SNAP-25)) was determined in surgical specimens obtained from normal proximal and aganglionic distal segments of the colon 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 bundles were detected in the submucosal layer and myenteric layer by NSF, SNAP, synaptotagmin, synaptobrevin, and SNAP-25. However, HPC-1/syntaxin 1A was not recognized in the proliferated nerve fibers of the submucosal layer or the hypertrophied nerve bundles of the aganglionic segment. These findings show that immunoreactivity of HPC-1/syntaxin 1A was decreased in the affected bowel segments of patients with HD and may be related to the pathogenesis of extrinsic nerve-fiber proliferation in the aganglionic colon of HD.
Nirasawa
Y
Y
Department of Pediatric Surgery, Kyroin University School of Medicine, Mitakashi, Tokyo, Japan. nirasawa@kyorin-u.ac.jp
Ito
Y
Y
Fujiwara
T
T
Seki
N
N
Tanaka
H
H
Akagawa
K
K
D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism; D003106:Colon / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006627:Hirschsprung Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007223:Infant; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D052066:N-Ethylmaleimide-Sensitive Proteins; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013368:Submucous Plexus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050857:Synaptotagmins; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C494212:STX1A protein, human; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins; D052066:N-Ethylmaleimide-Sensitive Proteins