GROWTH-ASSOCIATED PROTEIN-43 AND PROTEIN GENE-PRODUCT-9.5 INNERVATIONIN HUMAN PANCREAS - CHANGES IN CHRONIC-PANCREATITIS

Growth-associated protein-43, an established marker of neuronal elasti city during development and in injury, was used to characterize innerv ation in the normal human pancreas and changes in chronic alcohol-indu ced pancreatitis by using light microscopic immunocytochemistry and co mputer-assisted image analysis. Immunostaining for the pan-neuronal ma rker protein gene-product 9.5 served as a reference for the characteri zation of total innervation in both groups. In normal human pancreas, strong protein gene-product 9.5 immunostaining revealed all nerve fibr es in nerve trunks, all neuronal cell bodies and the entire parenchyma l innervation. In contrast, growth-associated protein-43 immunoreactiv ity was restricted to a few nerve fibres in interlobular nerve trunks and to fine varicose nerve fibres supplying the parenchyma, blood vess els, pancreatic ducts and intrinsic ganglia. In cell bodies of intrins ic neurons, growth-associated protein-43 immunoreactivity was absent o r extremely faint. In chronic pancreatitis, the protein gene-product 9 .5 innervation exhibited region-specific changes. In areas with reduce d parenchyma, the protein gene-product 9.5 innervation was sparse. In fibrotic regions, which are characteristic for advanced stages of chro nic pancreatitis, enlarged nerve trunks showing neuroma-like formation s were heavily stained for protein gene-product 9.5. In fibrotic tissu e, protein gene-product 9.5-containing nerve fibres were extremely rar e. The growth-associated protein-43 innervation in chronic pancreatiti s was Characterized by a dramatic increase, which was most pronounced in the enlarged nerve trunks. Such nerve trunks were frequently surrou nded by infiltrates of immune cells, which in some cases formed follic le-like structures. Digital image analysis of adjacent sections and do uble fluorescence immunocytochemistry revealed that growth-associated protein-43 immunoreactivity was present in the vast majority of protei n gene-product 9.5-immunoreactive nerve fibres. In contrast to the nor mal 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 nerves suggests that the innervation of the normal human pancreas undergoes continual and t oposelective remodelling. The increase in the density of growth-associ ated protein-43 immunoreactive nerve fibres in enlarged nerve trunks p aralleled by augmented expression of growth-associated protein-43 in i ntrinsic neurons and reduced parenchymal growth-associated protein-43- immunoreactive innervation underline the dramatic plasticity of pancre atic innervation in chronic pancreatitis. Close spatial relationships of growth-associated protein-43-containing enlarged nerve bundles and fibres branching thereof with immune cells may suggest involvement of growth-associated protein-43 in local neuroimmune mechanisms, which ma y be related to the perpetuation of inflammatory pain and to the chang es in exocrine and endocrine functions in chronic pancreatitis.