Evidence of the participation of peribiliary mast cells in regulation of the peribiliary vascular plexus along the intrahepatic biliary tree
Evidence of the participation of peribiliary mast cells in regulation of the peribiliary vascular plexus along the intrahepatic biliary tree
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DOI：
10.1038/labinvest.3780106
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发表时间：
2000-07-01
影响因子：
5
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Koda, W;Harada, K;Nakanuma, Y
我们的初步研究表明，胰酶阳性的肥大细胞(MC)密集分布在肝内胆管(MC)周围。本研究观察了71例正常肝、24例慢性肝炎和45例肝硬变患者胆管周围微循环的病理生理学作用。类胰酶阳性MC与供肝内胆管树的胆管周围血管丛(PVP)的微血管非常接近。类胰蛋白酶阳性MC多见于包括周细胞在内的血管平滑肌细胞旁。通过超微结构分析，确定了类胰蛋白酶阳性MC的位置。在肝硬变中，PVP和胆管周围MC的微血管数量平行增加。胆管周围MC内皮素-1(ET-1)免疫反应阳性，组胺、糜酶、诱导型一氧化氮合酶(INOS)、内皮素A和B(ETA和ETB)受体呈不同程度的免疫阳性反应，尤其是在肝硬变中。在PVP的血管内皮细胞上，内皮型一氧化氮合酶(ENOS)和内皮型一氧化氮合酶(ET-1)的表达一致，ETA受体、ETB受体和iNOS的表达也不同。PVP周细胞除表达ET-1和iNOS外，还表达ETA和ETB受体。胆管上皮细胞还局部表达iNOS、ET-1、ETA和ETB受体。这些血管活性物质在肝硬变的细胞成分上呈强阳性表达。原位杂交法观察到iNOS免疫反应阳性细胞成分，包括胆管周围MC上有iNOS mRNA信号。这些形态和免疫组织化学结果表明，肝内胆管树周围显示血管活性物质的细胞成分在正常肝脏的PVP的血管调节中是非常动态的，在肝硬变中更是如此，胆管周围MC直接或间接地对PVP的微循环产生局部影响。缩写：Amex，丙酮，苯甲酸甲酯，二甲苯；ASMA，α-平滑肌肌动蛋白；ET，ET；ET-1，ET-1；ETA受体，ET A受体；ETB受体，ET 8受体；eNOS，内皮型一氧化氮合酶；MC，肥大细胞；MCT，类胰蛋白酶阳性，糜乳酶阴性的肥大细胞；MCTC，类胰蛋白酶阳性，糜酶阳性肥大细胞；NO，一氧化氮；iNOS，诱导型一氧化氮合酶；PBS，磷酸盐缓冲盐水；PVP，胆管周围血管丛；肿瘤坏死因子-α。
Our pilot study disclosed that trypase-positive mast cells (MC) were densely distributed around the intrahepatic bile ducts (peribiliary MC). In this study, the pathophysiologic roles of these MC were examined with respect to the microcirculation around the bile duct in 71 cases of histologically normal liver, 24 cases of chronic hepatitis, and 45 cases of liver cirrhosis. The tryptase-positive MC were very close to the microvessels of the peribiliary vascular plexus (PVP), which supply the intrahepatic biliary tree. The tryptase-positive MC were frequently found adjacent to vascular smooth muscle cells, including pericytes. The location of the tryptase-positive MC was confirmed by ultrastructural analysis. In cirrhosis, the numbers of both microvessels of PVP and peribiliary MC increased in parallel. Peribiliary MC were immunoreactive for endothelin 1 (ET-1), and were variably immunoreactive for histamine, chymase, inducible nitric oxide synthase (iNOS), and endothelin A and B (ETA and ETB) receptors, particularly in cirrhotic livers. On vascular endothelial cells of PVP, endothelial nitric oxide synthase (eNOS) and ET-1 were consistently detectable, and ETA receptors, ETB receptors, and iNOS were variably detectable. Pericytes of PVP expressed ETA and ETB receptors in addition to ET-1 and iNOS. Biliary epithelial cells also focally expressed iNOS, ET-1, and ETA and ETB receptors. These vasoactive substances were strongly expressed on the cellular components in cirrhotic liver. By in situ hybridization, iNOS mRNA signals were observed on iNOS-immunoreactive cell components, including peribiliary MC. These morphologic and immunohistochemical findings suggest that the cellular components displaying vasoactive substances in the milieu of the intrahepatic biliary tree are very dynamic in the vasoregulation of PVP in normal livers, even more so in cirrhosis, and that peribiliary MC exert local effects on the microcirculation of PVP, directly and indirectly. A list of abbreviations: AMeX, acetone, methyl benzoate, and xylene; ASMA, alpha-smooth muscle actin; ET, endothelin; ET-1, endothelin 1; ETA receptor, endothelin A receptor; ETB receptor, endothelin 8 receptor; eNOS, endothelial nitric oxide synthase; MC, mast cell; MCT, tryptase positive, chymase negative mast cells; MCTC, tryptase positive, chymase positive mast cells; NO, nitric oxide; iNOS, inducible nitric oxide synthase; PBS, phosphate buffer saline; PVP, peribiliary vascular plexus; TNF-, tumor necrosis factor alpha.