GROWTH-ASSOCIATED PROTEIN-43 AND PROTEIN GENE-PRODUCT-9.5 INNERVATION IN HUMAN PANCREAS - CHANGES IN CHRONIC-PANCREATITIS
GROWTH-ASSOCIATED PROTEIN-43 AND PROTEIN GENE-PRODUCT-9.5 INNERVATION IN HUMAN PANCREAS - CHANGES IN CHRONIC-PANCREATITIS
复制标题
DOI：
10.1016/0306-4522(94)90020-5
复制
发表时间：
1994-11-01
期刊：
影响因子：
3.3
通讯作者：
WEIHE, E
中科院分区：
文献类型：
--
作者：
FINK, T;DISEBASTIANO, P;WEIHE, E
生长相关蛋白-43是神经发育和损伤过程中神经元弹性的标记物，通过光镜免疫细胞化学和计算机辅助图像分析，用来表征正常人胰腺的神经支配和慢性酒精性胰腺炎的变化。泛神经元标志物蛋白基因产物9.5的免疫组织化学染色可作为两组总神经支配特征的参考。在正常人胰腺中，强蛋白基因产物9.5免疫组织化学染色显示神经干中的所有神经纤维、所有神经元胞体和整个实质神经支配。相反，生长相关蛋白-43免疫反应仅限于小叶间神经干中的少数神经纤维和供应实质、血管、胰管和内脏神经节的细小静脉曲张神经纤维。在内源性神经元胞体中，生长相关蛋白-43免疫反应缺失或极弱。在慢性胰腺炎中，蛋白基因产物9.5的神经支配表现出区域特异性的变化。在实质减少的区域，蛋白基因产物9.5的神经支配稀疏。在慢性胰腺炎晚期的纤维化区，显示神经瘤样结构的扩大的神经干被蛋白质基因产物9.5浓染。在纤维化组织中，含有蛋白基因产物9.5的神经纤维极为罕见。生长相关蛋白-43在慢性胰腺炎中的神经支配以显著增加为特征，在扩大的神经干中最为明显。这类神经干通常被免疫细胞的渗入所包围，在某些情况下，免疫细胞会形成滤泡状结构。相邻切片的数字图像分析和双荧光免疫细胞化学显示，生长相关蛋白-43免疫反应存在于绝大多数蛋白基因产物9.5-免疫反应神经纤维中。与正常胰腺相比，主要的内源性神经元亚群表达生长相关蛋白-43。生长相关蛋白-43在胰腺神经终末区域的表达表明，正常胰腺的神经支配经历了连续和局部选择性的重塑。在扩大的神经干中生长相关蛋白-43免疫反应神经纤维的密度增加，同时伴随着生长相关蛋白-43在内源性神经元中表达的增加和实质生长相关蛋白-43免疫反应神经分布的减少，突显了慢性胰腺炎胰腺神经支配的显著可塑性。生长相关蛋白-43表达的神经束及其分支与免疫细胞的空间关系密切，提示生长相关蛋白-43参与局部神经免疫机制，可能与慢性胰腺炎时炎性疼痛的持续存在及外、内分泌功能的改变有关。
Growth-associated protein-43, an established marker of neuronal elasticity 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 nerves 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. 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 may be related to the perpetuation of inflammatory pain and to the changes in exocrine and endocrine functions in chronic pancreatitis.