• Biomolecules & Therapeutics
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• 제3권3호
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• pp.188-191
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• 1995

The Present study was undertaken to indicate the major source of NO by liver cells in vitro. Even at early stages of induction or low LPS concentrations, NO was produced at high rates by LPS(Lipopolysaccharide) on the isolated rat kupffer cells. PMA(phorbol 12-myristate 13-acetate) induced NO formation at low rates in the same cells. IFN-${\gamma}$ (Interferon-${\gamma}$) alone had not induced NO formation but it stimulated the effects of LPS. Calcium ionophore A23187 caused no stimulatory effect. It suggests that LPS has especially strong NO inducer on the kupffer cells and its mechanism is related to those on macrophage in other organs. In other nonparenchymal liver cells, sinusoidal endothelial cells were not stimulated to produce NO either by inducers of aortic endothelium(A23187, ATP and ADP) or by effectors of macrophages(LPS, IFN-${\gamma}$. This results suggest that rat liver kupffer cells appear to be the major source of NO by liver cells in vitro. But in vivo, liver endothelial cells may still be capable of producing NO. Furthermore, kupffer cells may produce factors that facilitate NO production by the endothelial cells.

• Applied Microscopy
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• 제12권1호
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• pp.11-21
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• 1982

A number of recent ultrastructural studies have shown marked differences between the two lining cell types in adult liver sinusoids, endothelial cells and Kupffer cells. In the present study, the ultrastructural features and electron microscopic cytochemistry of sinusoidal lining cells in the fetal liver were studied through fetal period to neonate in the rat. At fetal period, the sinusoid, which contains various blood component, in lined by the endothelial cells, the Kupffer cells and the fat storing cells that located in the space of Disse. As gestation proceeded, these eel's are arranged as adult liver sinusoids. The sinusoidal wall appears to be discontinuous with open fenestration between endothelial cells, but no basal lamina can observed. It seems to be morphologically and functionally distinct at the early gestation between the endothelial cells and the Kupffer cells, the latter showing marked phagocytized activity. The fat storing cells, which contain several fat droplets, are located in the space of Disse. Ultrastructural localization of the acid and alkaline phosphatase activity were noted on the sinusoidal lining cells.

• Applied Microscopy
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• 제23권2호
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• pp.41-52
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• 1993

본 연구에서는 반수서동물인 Suncus Murinus간실질의 구조와 간소엽에 존재하는 간실질세포, 동모양내피 세포, Kupffer세포 및 Ito세포의 미세구조를 관찰하고 이들의 특징을 포유동물 및 비포유동물의 것들과 비교 고찰하였다. 간실질세포는 지방소적과 비교적 큰 사립체를 많이 함유하고 있었으며 세포간격은 좁았으나 세포 표면은 가늘고 긴 돌기를 많이 갖고 있어 그 미세구조가 비포유동물의 일부 동물종에 유사한 소견을 나타냈다. 내피세포 또한 일부 비포유동물에 있어서와 같이 용해소체를 많이 함유하고 있어 Kupffer세포와의 식별이 어려웠다. 간소엽에는 담세관이 많았으며 일부 담세관과 담관은 Disse강에서 관찰되었는데 이러한 담관계는 Disse강에 있는 소세포와 간실질세포에 의해서 형성되어있거나 소세포들이 내강을 둘러 싸면서 형성하고 있었다. 담관계형성에 관여하는 소세포들은 지방소적을 함유하거나 함유하지 않은 Ito세포일 것으로 추정되었다. 이상의 소견으로 미루어 Suncus Murinus간장은 포유동물과 비포유동물의 구조와 미세구조를 동시에 갖추고 있는 것같이 보인다.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.111-117
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• 2004

Hepatic microcirculatory failure is a major component of reperfusion injury in the liver. Recent data provided some evidence that endothelium-derived vasoconstrictors and vasodilators may be functionally important to the control of the total hepatic blood flow under these conditions of circulatory failure. Since Kupffer cells provide signals that regulate the hepatic response in ischemia/reperfusion (I/R), the aim of this study was to investigate the role of Kupffer cells in the I/R-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. The Kupffer cells were inactivated by gadolinium chloride ($GdCl_3$, 7.5 mg/kg body weight, intravenously) 1 day prior to ischemia. Liver samples were obtained 5 hrs after reperfusion for RT-PCR analysis of the mRNA for genes of interest: endothelin-1 (ET-1), its receptors $ET_A and ET_B$, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). ET-1 mRNA expression was increased by I/R. mRNA levels for $ET_A$ receptors showed no change, whereas $ET_B$ receptor transcripts increased in the I/R group. The increases in ET-1 and $ET_B$ mRNA were not prevented by the $GdCI_3$ pretreatment. The mRNA levels for iNOS and eNOS significantly increased within the I/R group with no significant difference between the I/R group and the $GdCl_3$-treated I/R group. HO-1 mRNA expression significantly increased in the I/R group and this increase was attenuated by $GdCI_3$. In conclusion, we have demonstrated that an imbalance in hepatic vasoregulatory gene expression occurs during I/R. Our findings suggest that the activation of Kupffer cells is not required for I/R-induced hepatic microvascular dysfunction.

• Applied Microscopy
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• 제29권1호
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• pp.43-56
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• 1999

태생기 간 적혈구형성 중 혈관밖공간의 미성숙 적혈구모세포의 일부는 동굴모세혈관 속공간으로 이주하며, 별큰포식세포에 의해 영향을 받는다. 본 연구에서는 혈관속공간에 이주한 미성숙 적혈구모세포와 별큰포식세포의 관계를 규명하고자 간 적혈구형성의 활성도가 높게 유지되는 태령 제 11주부터 태령 제 20주에 이르는 태아 간과 쥐 태자 간의 연구재료를 대상으로 투과 및 주사전자현미경 관찰을 통해 다음과 같은 결론을 얻었다. 1) 별큰포식세포는 성인 간이나 다른 태령 시기에 비해 비대하였고 많은 세포질돌기들을 갖고 있었다. 이 세포는 부분적으로 세포분열에 의해 증식되고 있었으며 성인 간의 별큰포식세포와 다르게 자가종식을 할 수 있었다. 3) 호산성적혈구모세포에서 탈출된 핵은 별큰포식세포의 속공간쪽과 간세포쪽 세포막에서 포식되었다. 포식된 핵은 주변 부위에 층판이 형성되거나 및 개의 작은 조각으로 파괴되는 등 다양한 소화과정을 보였다. 3) 동굴모세혈관 속공간에서 별큰포식세포는 미성숙적혈구모세포들과 직접으로 접촉하거나, 미성숙 적혈구 모세포들 사이에 별큰포식세포의 긴 세포질돌기가 뻗쳐 있어 골수 적혈구형성에서 관찰되는 적혈구모세포섬과 비슷하였다. 이상의 결과를 종합하면 태아 간 적혈구형성이 왕성한 시기의 별큰포식세포는 적혈구를 포식하는 것 외에도, 세포가 비대해져서 동굴모세혈관을 통한 혈액흐름을 감소시키고, 적혈구모세포섬을 구성하여 태아 간 적혈구형성에서 미성숙 적혈구모세포의 성숙과 관련된 기계적 및 생리학적 기능을 수행한다고 생각된다.

• 대한수의학회지
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• 제32권2호
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• pp.207-210
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• 1992

Enterovirus감염 돼지의 감염초기 virus의 동태를 규명하고자 초유를 섭취하지 않는 1~2일령의 돼지에 돼지 enterovirus 3형을 경구감염시킨후 간조직을 전자현미경으로 관찰하였던 바 다음과 같은 결과를 얻었다. 감염후 3일째 부검한 돼지의 간에서 간세포의 심한 공포변성이 인정되었고 간 동양혈관 내피세포 및 Kupffer세포에서 picornavirus의 특징적인 virus결정이 출현하였으며 확장된 ER은 virus 결정과 밀접하게 관련되어 있었다. 또한 동양혈관 세포와 간세포에서는 미숙한 virus모양의 입자들로 구성된 세포질내 봉입체가 관찰되기도 하였다. 이상의 소견으로 보아 돼지 enterovirus 3형은 신경친화성 뿐만 아니라 감염초기 간에 친화성이 큰 것으로 생각된다.

• Toxicological Research
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• 제21권2호
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• pp.141-150
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• 2005

1,3-Dichloro-2-propanol (1,3-DCP) is known as chloride chemicals and causes severe hepatotoxic agent. The Ito cells and Kupffer's cells of the liver in the 5 old F344 Rats were exposed to 1,3-DCP gas chamber for 6 hours/ a day, 5 days/ a week, and 13 weeks, in the 0, 5, 20, 80 ppm, respectively. After then the body weights, liver weights, and relative liver weight to body weight were measured, and the hepatic tissues were prepared by the routine and Immunostain method, and observed by the LM, and EM. In the results, there were severe body weight decrease (p<0.05) in the 80 ppm of the male and female rats. The relative liver weights to the body weight were increased relate with exposed 1,3-DCP concentration (P<0.001). Inflammatory cells, infiltration was observed at the perivascular area in the 20 ppm exposed group, and bilirubin pigment infiltration, bile duct hyperplasia, inflammation hepatocytic necrosis, fibrosis were observed in the 80 ppm exposure group. In the 80 ppm exposure group, disarrangement of the endothelial cells, erythrocytes and hepatic cell fragment in the Disse space and numerous migration macrophages were observed in the necrotic area by EM observation. In the immunostained hepatic tissues positive stained ED1 cells were extremely increased (P<0.05) in central vein area, but ED2 was weakly positive immunostained in the 80 ppm exposed group. Immunostained desmin was observed in the Ito cell. It was no difference in the low and medium exposed group but it was typical increase in the necrotic area. In conclusion, These results suggest that NOAEL of 1,3-DCP may be 5 ppm in rats and the Immunostained of desmin, ED1 and ED2 positive cells activated in the inflammatory liver were related to the exposure volume and density. The increase of the Ito cells were related to the severe phagocytosis of the Kupffer's cells.

• 대한수의학회지
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• 제16권2호
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• pp.141-150
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• 1976

In order to know the morphological changes of liver in nitrate poisoning, the ultrastructural studies were carried out on the rabbit liver after potassium nitrate was administered orally at lethal dose, in single treatment, as acute case and at two different levels. 1.0 and 0.5g/kg of body weight daily for 43 and 60 days as chronic case, respectively, The results were summarized as followings: 1. In the hepatic cells of acute case, mitochondria were swollen, disappearance of cristae and variable in shape. Dilatation of rough endoplasmic reticulum and vacuoles containing degenerated cell organells were observed. Glyogen particles were decreased in number. Degenerated Kupffer cells were often seen in acute case. 2. In the hepatic cells of chronic case, there were increase of smooth endoplasmic reticulum, marked enlargement of rough endcplasmic reticulum, detachment of membrane bound ribosome and some rough endoplasmic reticulum changed into smooth endoplasmic reticulum. Secondary lysosome, abundant glycogen paricles and myelin-figure structures were also observed in the cytoplasm of the hepatic cells. The endothelial cells were proliferated in the area of the necrotic cells.

• 대한의생명과학회지
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• 제8권3호
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• pp.179-184
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• 2002

We investigated the morphological changes and TUNEL reaction of apoptotic cells in the liver of D-galactosamine (20 mg/mouse) and lipopolysaccharide (5 $\mu\textrm{g}$/mouse)-treated 30 mice (BALB/c), and in additioa also of apoptotic cells in kidney and spleen. The livers and other some organs of mice at 6, 12, 24, 48 and 72 hrs after treatment were collected and were fixed with 10% neutral formalin and paraffin sections were stained with hematoxylin-eosin or terminal deoxynucleotidly transferase-mediated dUTP nick end labeling (TUNEL) method. Morphological changes in apoptotic hepatocytes were chondensation of nuclei and density of cytoplasms, then the margination and pyknosis of chromatin, the formation of half-moon- or horse-shoe- or ship-like shapes of condensed chromatin mass, lastly formation of apoptotic bodies, disappearance of nuclear envelopes, decrease of stainability, then lysis and disappearance of apoptotic bodies. TUNEL positive reactions of hepatocytes were appeared first moderate in uncondensed hepatocytes, severe in condensed hepatocytes, moderate in chromatin-marginated hepatocytes. These reactions also were appeared moderate in hepatocytes with half-moon- or horse-shoe- or ship-like pyknotic chromatin mass or apoptotic bodies, and mild or negative in hepatocytes with lysed apoptotic bodies or with disappeared nuclear envelopes. Consequently these results suggested that TUNEL positive reactions of hepatocytes appeared at more early stages than appearance of chromatin condensation and disappeared at more early stage than disappearance of histological findings of apoptosis. We also confirmed that the differentiation of apoptotic cells from normal healthy cells of Kupffer cells and vascular endothelial cells in liver, reticular cells and lymphocytes in spleen and epithelial cells of tubules and ducts in kidney was impossible in H-E preparations but was possible in TUNEL preparations.

• BMB Reports
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• 제55권12호
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• pp.633-638
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• 2022

Liver regeneration is a well-known systemic homeostatic phenomenon. The N⁶-methyladenosine (m⁶A) modification pathway has been associated with liver regeneration and hepatocellular carcinoma. m⁶A methyltransferases, such as methyltransferase 3 (METTL3) and methyltransferase 14 (METTL14), are involved in the hepatocyte-specific-regenerative pathway. To illustrate the role of METTL14, secreted from non-parenchymal liver cells, in the initiation phase of liver regeneration, we performed 70% partial hepatectomy (PH) in Mettl14 heterozygous (HET) and wild-type (WT) mice. Next, we analyzed the ratio of liver weight to body weight and the expression of mitogenic stimulators derived from non-parenchymal liver cells. Furthermore, we evaluated the expression of cell cycle-related genes and the hepatocyte proliferation rate via MKI67-immunostaining. During regeneration after PH, the weight ratio was lower in Mettl14 HET mice compared to WT mice. The expressions of hepatocyte growth factor (HGF) and tumor necrosis factor (TNF)-α, mitogens derived from non-parenchymal liver cells that stimulate the cell cycle, as well as the expressions of cyclin B1 and D1, which regulate the cell cycle, and the number of MKI67-positive cells, which indicate proliferative hepatocyte in the late G1-M phase, were significantly reduced in Mettl14 HET mice 72 h after PH. Our findings demonstrate that global Mettl14 mutation may interrupt the homeostasis of liver regeneration after an acute injury like PH by restraining certain mitogens, such as HGF and TNF-α, derived from sinusoidal endothelial cells, stellate cells, and Kupffer cells. These results provide new insights into the role of METTL14 in the clinical treatment strategies of liver disease.