Mechanism for a dendritic cell transport in the hepatic sinusoids and lymph.

本研究的目的：肝脏是不断调查的交通抗原呈递树突状细胞（DC）。本实验研究了DC在肝微结构内的转运系统及其调控因素。静脉内转移的大鼠DC移位并选择性地积聚在肝淋巴结的副皮质中（已发表）。大鼠肝移植后不久，供者MHCII+细胞向脾脏T和B细胞区迁移。肝淋巴液渗漏入腹腔，淋巴液中的DC被吸收入肠系膜淋巴丛，并转运至前纵隔淋巴结，推测供体MHCII+细胞可能对应于肝脏中的DC祖细胞（制备中）。将大量大鼠DC静脉注射到同种异体宿主体内，动态追踪DC在肝组织中的命运。我们发现DC首先被枯否细胞捕获在窦壁中，可能是通过机械和分子相互作用。捕获的DC可能溢出到Disse间隙中，然后离开肝小叶进入门管区的组织间隙。最终这些细胞可能爬进位于汇管区的毛细淋巴管（在第103届日本解剖学大会上发表）。这将通过与庆应义塾大学的末松博士合作使用共聚焦激光显微荧光照相术进行体内观察来确定（目前正在研究中）。在正常大鼠的窦状隙区，DC和枯否细胞之间经常观察到密切的联系。肝窦中的大鼠枯否细胞能够在体内和体外选择性地从血液中捕获DC（已发表），表明存在某些粘附分子，可能是糖残基和leetins。通过这种方式，DC可以附着在正弦壁上，这可能是外渗的前奏。目前正在与T.Suganuma博士合作进行研究。宫崎医科大学。

Aim of this study : Liver is constantly surveyed by a traffic of antigen-presenting dendritic cells (DC). We studied about the transport system of DC within the liver microarehitecture and factors which regulate this transport.Result 1. intravenously transferrd rat DC translocated and selectively accumulated in the paracortex of the hepatic lymph nodes (published). Soon after the rat liver transplantation, donor MHCII+ cells migrated to both T and B cell areas of thc spleen. The hepatic lymph leaked into the peritoncal cavity and DC in lymph were absorbed into diaphragmatic lymph plexus and transported to the anterior mediastinal LN.Donor MHCII+ cells arc speculated to correspond to DC progenitors in the liver (in preparation).Result 2. A large number of rat DC were injected intravenously to allogencic host and a fate of the DC in the liver tissue was traced lime kinetically. We found that DC were first entrapped by the Kupffer cells in the sinusoidal wall possibly through mechanical and molecular interactions. The entrapped DC may extravasate into the Disse's space and then exit the hepatic lobule into tissue space of the portal area. Eventually these cells probably crawl into the lymphatic capillary located in the portal area (presented at 103rd Japanese Anatomy Congress). This will be confinned by in vivo observation using confocal laser microlluorography by a collaboration with Dr. M.Suematsu, Keio University (now under study).Result 3. In the sinusoidal area a close association between the DC and Kupffer cells is often observed in normal rats. Rat Kupffer cells in the hepatie sinusoids are capable of selectively trapping DC from the blood in vivo and in vitro (published) suggesting a presence of certain adhesion molecules, possibly sugar residues and leetins. By this, DC could attach to the sinusoidal wail probably as a prelude to extravasation. This is now under study by collaborating with Dr. T.Suganuma. Miyazaki Medical College.