Study on the regulation mechanism by endogenous bioactive substances produced by hepato-sinusoidal cells.

肝窦细胞主要由Kupffer细胞、肝窦内皮细胞、Ito细胞和窝细胞组成。本研究以Kupffer细胞和肝窦内皮细胞为研究对象，分析内源性活化物质对肝脏调节网络的作用。1)肝窦细胞产生花生四酸代谢物和脂质代谢物。当大鼠Kupffer细胞受到脂多糖（LPS）、热杀痤疮丙酸杆菌（P. acnes）和OK-432等生物反应调节剂刺激后，它们产生并分泌前列腺素（PG） E2、6-酮pgf1 α和血栓素（TX）B2。然而，它们在静息状态下产生PGD2。这种变化是由于位于PG代谢途径上游的环加氧酶的诱导。受刺激的Kupffer细胞不产生PG代谢物，除非没有Ca^<2+>，或者Ca^<2+>-乳糜酸盐或钙调素抑制剂，这表明受刺激的Kupffer细胞产生PG代谢物可能取决于细胞内和细胞外的Ca以及钙调素。当库普弗细胞和肝窦内皮细胞与钙离子载体孵育时，它们产生血小板活化因子（PAF），一种生物活性脂质代谢物。2)肝窦细胞产生的细胞因子。lps刺激的Kupffer细胞产生白细胞介素(IL)-1、IL-6和肿瘤坏死因子(TNF)- α。受刺激的肝窦内皮细胞也观察到这一点。干扰素- γ，一种巨噬细胞激活因子，导致Kupffer细胞产生这些细胞因子，而PGE1或PGI2则减少这些细胞因子的产生。提示肝窦细胞细胞因子网络和花生酸代谢物级联之间存在着相互调控和内部调控的系统。

Hepatic sinusoidal cells are mainly constituted by Kupffer cells, hepatic sinusoidal endothelial cells, Ito cells and pit cells. In this study, we focused Kupffer cells and hepatic sinusoidal endothelial cells to analyze the role of endogenous activating substances on the regulation network in the liver.1) The production of arachidic acid metabolites and lipid metabolites by hepatic sinusoidal cells. Once rat Kupffer cells were stimulated by biological response modifiers such as lipopolysaccharide (LPS), heat-killed Propionibacterium acnes (P. acnes) and OK-432, they produced and secreted prostaglandin (PG) E2, 6-keto PGF1alpha and thromboxane (TX)B2. However, they produced PGD2 in rest state. This change was due to the induction of cyclo-oxygenase that is located on the upstream of the PG metabolic pathway. The stimulated Kupffer cells did not produce such PG metabolites unless they were inculated without Ca^<2+>, or with Ca^<2+>-chylates or calmodulin inhibitors, suggesting that their production by stimulated Kupffer cells might depend on intracellular and extracellular Ca as well as calmodulin. When Kupffer cells and hepatic sinusoidal endothelial cells were incubated with Ca ionophore, they produced platelet activating factor (PAF), a biological active lipid metabolite.2) Cytokines produced by hepatic sinusoidal cells. LPS-stimulated Kupffer cells produced interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha. This was also obsereved by stimulated hepatic sinusoidal endothelial cells. Interferon-gamma, a macrophage activating factor, led Kupffer cells to produce these cytokines, while PGE1 or PGI2 reduced such cytokine production. These results suggested the existence of the inter-and intra-regulation systems among cytokine network and arachidic acid metabolite cascade in the hepatic sinusoidal cells.