Growth-associated protein-43 and protein gene-product 9.5 innervation in human pancreas: changes in chronic pancreatitis.
Growth-associated protein-43, an established marker of neuronal plasticity during development and in injury, was used to characterize innervation in the normal human pancreas and changes in chronic alcohol-induced pancreatitis by using light microscopic immunocytochemistry and computer-assisted image analysis. Immunostaining for the pan-neuronal marker protein gene-product 9.5 served as a reference for the characterization of total innervation in both groups. In normal human pancreas, strong protein gene-product 9.5 immunostaining revealed all nerve fibres in nerve trunks, all neuronal cell bodies and the entire parenchymal innervation. In contrast, growth-associated protein-43 immunoreactivity was restricted to a few nerve fibres in interlobular nerve trunks and to fine varicose nerve fibres supplying the parenchyma, blood vessels, pancreatic ducts and intrinsic ganglia. In cell bodies of intrinsic neurons, growth-associated protein-43 immunoreactivity was absent or extremely faint. In chronic pancreatitis, the protein gene-product 9.5 innervation exhibited region-specific changes. In areas with reduced parenchyma, the protein gene-product 9.5 innervation was sparse. In fibrotic regions, which are characteristic for advanced stages of chronic pancreatitis, enlarged nerve trunks showing neuroma-like formations were heavily stained for protein gene-product 9.5. In fibrotic tissue, protein gene-product 9.5-containing nerve fibres were extremely rare. The growth-associated protein-43 innervation in chronic pancreatitis was characterized by a dramatic increase, which was most pronounced in the enlarged nerve trunks. Such nerve trunks were frequently surrounded by infiltrates of immune cells, which in some cases formed follicle-like structures. Digital image analysis of adjacent sections and double fluorescence immunocytochemistry revealed that growth-associated protein-43 immunoreactivity was present in the vast majority of protein gene-product 9.5-immunoreactive nerve fibres. In contrast to the normal pancreas, a major subpopulation of intrinsic neurons immunostained for growth-associated protein-43. The expression of growth-associated protein-43 in the terminal fields of pancreatic nerve suggests that the innervation of the normal human pancreas undergoes continual and toposelective remodelling. The increase in the density of growth-associated protein-43 immunoreactive nerve fibres in enlarged nerve trunks paralleled by augmented expression of growth-associated protein-43 in intrinsic neurons and reduced parenchymal growth-associated protein-43-immunoreactive innervation underline the dramatic plasticity of pancreatic innervation in chronic pancreatitis.(ABSTRACT TRUNCATED AT 400 WORDS)
Fink
T
T
Department of Anatomy, University of Mainz, Germany.
Di Sebastiano
P
P
Büchler
M
M
Beger
H G
HG
Weihe
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D019922:GAP-43 Protein; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010179:Pancreas / Q000294:innervation* / Q000378:metabolism* / Q000601:surgery; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D013869:Thiolester Hydrolases / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase