The Experts below are selected from a list of 3459 Experts worldwide ranked by ideXlab platform
Pierrealain Clavien - One of the best experts on this subject based on the ideXlab platform.
-
synergism between platelets and leukocytes in inducing Endothelial Cell apoptosis in the cold ischemic rat liver a kupffer Cell mediated injury
The FASEB Journal, 2001Co-Authors: David Sindram, Robert J Porte, Maureane Hoffman, Rex C Bentley, Pierrealain ClavienAbstract:SPECIFIC AIMSThe first aim of this study was to investigate the effects of platelets and leukocytes on Sinusoidal Endothelial Cell apoptosis in the cold ischemic liver. Second, we studied the role ...
-
platelets induce Sinusoidal Endothelial Cell apoptosis upon reperfusion of the cold ischemic rat liver
Gastroenterology, 2000Co-Authors: David Sindram, Robert J Porte, Maureane Hoffman, Rex C Bentley, Pierrealain ClavienAbstract:Abstract Background & Aims: Sinusoidal Endothelial Cell (SEC) apoptosis is a central feature of reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation with possible deleterious effects. We tested the hypothesis that platelets mediate SEC apoptosis. Methods: Livers were perfused after 24 hours of cold preservation in University of Wisconsin solution in an isolated perfused rat liver model. The perfusate contained isolated syngeneic red blood Cells and purified platelets. Effects of inhibiting platelet adhesion on SEC apoptosis was tested using sialyl Lewis-X oligosaccharide (sLe x ), a natural ligand of selectin adhesion molecules. Reperfusion injury was assessed by established markers of injury. Apoptosis was determined by TUNEL and electron microscopy. Results: A third of the circulating platelets was rapidly sequestered in the liver after reperfusion. This was associated with increased graft injury. Single platelets were adherent to Sinusoidal lining without morphological or dynamic evidence of impairment of microcirculation. TUNEL staining revealed a 6-fold increase in the number of apoptotic SECs at 1 hour of reperfusion. No hepatocyte death or evidence of necrosis was detected up to 3 hours of reperfusion. Addition of sLe x inhibited adhesion and significantly reduced SEC apoptosis. Conclusions: Platelets cause SEC apoptosis upon reperfusion of liver grafts. Prevention of adhesion is protective. GASTROENTEROLOGY 2000;118:183-191
-
calpain inhibition prevents Sinusoidal Endothelial Cell apoptosis in the cold ischemic rat liver
Transplantation, 1999Co-Authors: David Sindram, Vivek Kohli, John F Madden, Pierrealain ClavienAbstract:Background. Cold preservation of the liver followed by reperfusion results in Sinusoidal Endothelial Cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. Methods. Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37°C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. Results. Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. Conclusion. Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation.
Laurie D. Deleve - One of the best experts on this subject based on the ideXlab platform.
-
liver Sinusoidal Endothelial Cell an update
Seminars in Liver Disease, 2017Co-Authors: Laurie D. Deleve, Ana C MarettimiraAbstract:This update focuses on two main topics. First, recent developments in our understanding of liver Sinusoidal Endothelial Cell (LSEC) function will be reviewed, specifically elimination of blood-borne waste, immunological function of LSECs, interaction of LSECs with liver metastases, LSECs and liver regeneration, and LSECs and hepatic fibrosis. Second, given the current emphasis on rigor and transparency in biomedical research, the update discusses the need for standardization of methods to demonstrate identity and purity of isolated LSECs, pitfalls in methods that might lead to a selection bias in the types of LSECs isolated, and questions about long-term culture of LSECs. Various surface markers used for immunomagnetic selection are reviewed.
-
hepatic vascular Endothelial growth factor regulates recruitment of rat liver Sinusoidal Endothelial Cell progenitor Cells
Gastroenterology, 2012Co-Authors: Lin Wang, Xiangdong Wang, Lei Wang, Jenny D Chiu, Gijs Van De Ven, William A Gaarde, Laurie D. DeleveAbstract:Background & Aims After liver injury, bone marrow–derived liver Sinusoidal Endothelial Cell progenitor Cells (BM SPCs) repopulate the sinusoid as liver Sinusoidal Endothelial Cells (LSECs). After partial hepatectomy, BM SPCs provide hepatocyte growth factor, promote hepatocyte proliferation, and are necessary for normal liver regeneration. We examined how hepatic vascular Endothelial growth factor (VEGF) regulates recruitment of BM SPCs and their effects on liver injury. Methods Rats were given injections of dimethylnitrosamine to induce liver injury, which was assessed by histology and transaminase assays. Recruitment of SPCs was analyzed by examining BM SPC proliferation, mobilization to the circulation, engraftment in liver, and development of fenestration (differentiation). Results Dimethylnitrosamine caused extensive denudation of LSECs at 24 hours, followed by centrilobular hemorrhagic necrosis at 48 hours. Proliferation of BM SPCs, the number of SPCs in the bone marrow, and mobilization of BM SPCs to the circulation increased 2- to 4-fold by 24 hours after injection of dimethylnitrosamine; within 5 days, 40% of all LSECs came from engrafted BM SPCs. Allogeneic resident SPCs, infused 24 hours after injection of dimethylnitrosamine, repopulated the sinusoid as LSECs and reduced liver injury. Expression of hepatic VEGF messenger RNA and protein increased 5-fold by 24 hours after dimethylnitrosamine injection. Knockdown of hepatic VEGF with antisense oligonucleotides completely prevented dimethylnitrosamine-induced proliferation of BM SPCs and their mobilization to the circulation, reduced their engraftment by 46%, completely prevented formation of fenestration after engraftment as LSECs, and exacerbated dimethylnitrosamine injury. Conclusions BM SPC recruitment is a repair response to dimethylnitrosamine liver injury in rats. Hepatic VEGF regulates recruitment of BM SPCs to liver and reduces this form of liver injury.
-
liver Sinusoidal Endothelial Cell progenitor Cells promote liver regeneration in rats
Journal of Clinical Investigation, 2012Co-Authors: Lin Wang, Xiangdong Wang, Guanhua Xie, Lei Wang, C K Hill, Laurie D. DeleveAbstract:The ability of the liver to regenerate is crucial to protect liver function after injury and during chronic disease. Increases in hepatocyte growth factor (HGF) in liver Sinusoidal Endothelial Cells (LSECs) are thought to drive liver regeneration. However, in contrast to Endothelial progenitor Cells, mature LSECs express little HGF. Therefore, we sought to establish in rats whether liver injury causes BM LSEC progenitor Cells to engraft in the liver and provide increased levels of HGF and to examine the relative contribution of resident and BM LSEC progenitors. LSEC label-retaining Cells and progenitors were identified in liver and LSEC progenitors in BM. BM LSEC progenitors did not contribute to normal LSEC turnover in the liver. However, after partial hepatectomy, BM LSEC progenitor proliferation and mobilization to the circulation doubled. In the liver, one-quarter of the LSECs were BM derived, and BM LSEC progenitors differentiated into fenestrated LSECs. When irradiated rats underwent partial hepatectomy, liver regeneration was compromised, but infusion of LSEC progenitors rescued the defect. Further analysis revealed that BM LSEC progenitors expressed substantially more HGF and were more proliferative than resident LSEC progenitors after partial hepatectomy. Resident LSEC progenitors within their niche may play a smaller role in recovery from partial hepatectomy than BM LSEC progenitors, but, when infused after injury, these progenitors engrafted and expanded markedly over a 2-month period. In conclusion, LSEC progenitor Cells are present in liver and BM, and recruitment of BM LSEC progenitors is necessary for normal liver regeneration.
-
vascular liver disease and the liver Sinusoidal Endothelial Cell
2011Co-Authors: Laurie D. DeleveAbstract:The hepatic Sinusoidal Endothelial Cell is highly differentiated, with unique morphology and function. It provides a porous barrier that facilitates access of the hepatocyte to oxygen and small molecules in the microcirculation. Other specialized functions include clearance of colloids and macromolecules, promotion of hepatic stellate Cell quiescence, and induction of immune tolerance. The hepatic Sinusoidal Endothelial Cell may be injured by a variety of toxins, ischemia–reperfusion, and even bacteria, leading to vascular liver diseases such as Sinusoidal obstruction syndrome, nodular regenerative hyperplasia, and peliosis hepatis.
-
structured illumination microscopy applications towards liver Sinusoidal Endothelial Cell fenestrations and hiv 1 Cell to Cell transmission
Asia Communications and Photonics conference and Exhibition, 2010Co-Authors: Gregory P Mcnerney, David G. Le Couteur, Laurie D. Deleve, Victoria C Cogger, Cristina Ionica Oie, Peter Mccourt, Bard Smedsrod, Wolfgang Hubner, Deanna L Thompson, Benjamin M DaleAbstract:In the last decade, the field of far-field super-resolution fluorescence microscopy exploded with multiple schemes for sub-diffraction-limit optical microscopy, culminating in a 2008 Method of the Year designation by Nature Publishing Group. Three general categories now exist: structured illumination microscopy (SIM), localization methods (e.g. PALM, dSTORM, and DH-PSF), and stimulated emission depletion (STED). Linear 3D structured illumination microscopy (3D-SIM) provides a factor of two in terms of lateral resolution gain (∼110 nm) when compared to confocal microscopy, but in all 3 dimensions - while STED and localization methods have surpassed this, but are mostly limited to 2 dimensions. A particular highlight of 3D-SIM, though, is that it can image samples prepared with standard fluorophores at multiple colors simultaneously, which we will demonstrate on two particular examples. The first application relates to imaging of 80 – 250 nm pores in liver Sinusoidal Endothelial Cells that separate blood plasma from Cells and debris before the plasma encounters the underlying hepatocytes. These structures have previously only been accessible to electron microscopy, but somewhat hampered by its low throughput, sample fixation, and the difficulty to simultaneously label multiple structures for electron and atomic force microscopy. 3D-SIM helped us gain novel insights in the structure and function of these fragile Cellular structures. In another application of 3D-SIM, we investigated the problem of direct Cell-to-Cell transmission of HIV-1 via T Cell virological synapses. In this concept, an HIV-1 infected CD4+ T lymphocyte can engage another CD4+ T lymphocyte and form a stable, connective synapse between the Cells which promotes targeted assembly of new virus at the point of Cell contact leading to rapid passage of large quantities of viral particles into the target Cell. Previous studies using a natively fluorescent HIV-1 clone termed HIV Gag-iGFP and spinning disk confocal microscopy allowed seamless tracking of HIV-1 Cell-to-Cell transmission, but was hindered by the diffraction-limited resolution, which did not allow us to distinguish individual virus particles (for example, HIV-1 is ∼130 nm). To study this process in finer detail we employed 3D-SIM and gained several structural insights that will be discussed.
Kenji Fujiwara - One of the best experts on this subject based on the ideXlab platform.
-
expressions of vascular Endothelial growth factor in nonparenchymal as well as parenchymal Cells in rat liver after necrosis
Biochemical and Biophysical Research Communications, 1999Co-Authors: Keiko Ishikawa, Satoshi Mochida, Akihiko Ohno, Mie Inao, Hitoshi Ikeda, Masabumi Shibuya, Shoji Mashiba, Astushi Matsui, Kenji FujiwaraAbstract:Vascular Endothelial growth factor (VEGF) can induce proliferation of Sinusoidal Endothelial Cells. Its mRNA expression was increased in proliferating rat hepatocytes in primary culture. To clarify a role of VEGF in liver after necrosis, expressions of VEGF and its receptors were measured in the liver or liver Cells isolated from rats after carbon tetrachloride intoxication. Hepatic VEGF mRNA expression increased later than 24 h after the intoxication and became prominent at 168 h when liver necrosis disappeared, while hepatic mRNA expressions of its receptors increased between 24 and 72 h. VEGF mRNA expression was increased in Kupffer Cells, hepatic macrophages and stellate Cells isolated from rats between 24 and 72 h after the intoxication and in hepatocytes at 168 h compared to those Cells from normal rats. Immunohistochemical VEGF stains were comparable to such results. Vascular Endothelial Cells existed abundantly in the necrotic areas, and Sinusoidal Endothelial Cells appeared following disappearance of the necrotic areas. VEGF mRNA expression in hepatocytes isolated from 70% resected liver was increased at 12 h after the operation and became marked between 72 and 168 h. Similar increase of hepatic VEGF expression was immunohistochemically seen. In conclusion, VEGF derives from nonparenchymal as well as parenchymal Cells in rat liver after necrosis. The former might contribute to vascular Endothelial Cell proliferation and the latter to Sinusoidal Endothelial Cell regeneration.
-
the mechanisms of hepatic Sinusoidal Endothelial Cell regeneration a possible communication system associated with vascular Endothelial growth factor in liver Cells
Journal of Gastroenterology and Hepatology, 1998Co-Authors: Satoshi Mochida, Keiko Ishikawa, Keiko Toshima, Mie Inao, Hitoshi Ikeda, Atsushi Matsui, Masabumi Shibuya, Kenji FujiwaraAbstract:Vascular Endothelial growth factor (VEGF) has been shown to induce proliferation of Sinusoidal Endothelial Cells in primary culture. To elucidate the mechanisms of Sinusoidal Endothelial Cell regeneration in vivo, mRNA expression of VEGF and its receptors, flt-1 and KDR/flk-1, were studied in rat livers. Northern blot analysis revealed that VEGF-mRNA was expressed in hepatocytes immediately after isolation from normal rats. In contrast, non-parenchymal Cells, including Sinusoidal Endothelial Cells, expressed VEGF receptor-mRNA. Vascular Endothelial growth factor-mRNA expression in hepatocytes was decreased during primary culture, but increased following a peak of DNA synthesis, induced by addition of epidermal growth factor or hepatocyte growth factor to the culture medium at 24 h of plating. In a 70% resected rat liver, VEGF-mRNA expression increased with a peak at 72 h after the operation, and mRNA expression of VEGF receptors between 72 and 168 h. In such a liver, mitosis was maximal in hepatocytes at 36 h and in Sinusoidal Endothelial Cells at 96 h. Also, mRNA expression of both VEGF and its receptors was significantly increased in carbon tetrachloride-intoxicated rat liver compared with normal rat liver. Vascular Endothelial growth factor expression was minimal in Kupffer Cells isolated from normal rats, but marked in activated Kupffer Cells and hepatic macrophages from the intoxicated rats. Vascular Endothelial growth factor-mRNA expression was also increased in activated stellate Cells from these rats and in the Cells activated during primary culture compared with quiescent Cells. We conclude that increased levels of VEGF expression in regenerating hepatocytes may contribute to the proliferation of Sinusoidal Endothelial Cells in partially resected rat liver, probably through VEGF receptors up-regulated on the Cells. Also, VEGF derived from activated Kupffer Cells, hepatic macrophages and stellate Cells may be involved in this proliferation in injured rat liver.
-
Sinusoidal Endothelial Cell damage by activated macrophages in rat liver necrosis
Gastroenterology, 1993Co-Authors: Masahiro Arai, Satoshi Mochida, Akihiko Ohno, Itsuro Ogata, Kenji FujiwaraAbstract:Abstract Background: Massive hepatic necrosis caused by fibrin deposition in the hepatic sinusoids develops with hepatic macrophage activation in rats given endotoxin after administration of heat-killed Corynebacterium parvum . Targeted Cells of such macrophages were investigated. In C. Parvum -treated rats, the pathological appe Methods: arance of liver Cells was serially measured in serum following endotoxin administration and compared with the appearance in the perfusate during closed liver perfusion with endotoxin. Results: Serum activities of tumor necrosis factor, purine nucleoside phosphorylase present in both hepatocytes and Sinusoidal Endothelial Cells, and levels of alanine aminotransferase were higher after 30 minutes, 1 hour, and 3 hours, respectively. Pretreatment of rats with gadolinium chloride, an inhibitor of macrophage function, reduced this liver injury. Although alanine aminotransferase activity remained almost unchanged in the liver perfusate, purine nucleoside phosphorylase activity increased. This increase was reduced when rats were pretreated with gadolinium chloride. There was Sinusoidal Endothelial Cell damage around hepatic macrophages in the liver perfused with endotoxin. Conclusions: Activated hepatic macrophages may cause Sinusoidal Endothelial Cell damage leading to hepatocyte necrosis in rats given C. parvum and endotoxin.
David Sindram - One of the best experts on this subject based on the ideXlab platform.
-
synergism between platelets and leukocytes in inducing Endothelial Cell apoptosis in the cold ischemic rat liver a kupffer Cell mediated injury
The FASEB Journal, 2001Co-Authors: David Sindram, Robert J Porte, Maureane Hoffman, Rex C Bentley, Pierrealain ClavienAbstract:SPECIFIC AIMSThe first aim of this study was to investigate the effects of platelets and leukocytes on Sinusoidal Endothelial Cell apoptosis in the cold ischemic liver. Second, we studied the role ...
-
platelets induce Sinusoidal Endothelial Cell apoptosis upon reperfusion of the cold ischemic rat liver
Gastroenterology, 2000Co-Authors: David Sindram, Robert J Porte, Maureane Hoffman, Rex C Bentley, Pierrealain ClavienAbstract:Abstract Background & Aims: Sinusoidal Endothelial Cell (SEC) apoptosis is a central feature of reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation with possible deleterious effects. We tested the hypothesis that platelets mediate SEC apoptosis. Methods: Livers were perfused after 24 hours of cold preservation in University of Wisconsin solution in an isolated perfused rat liver model. The perfusate contained isolated syngeneic red blood Cells and purified platelets. Effects of inhibiting platelet adhesion on SEC apoptosis was tested using sialyl Lewis-X oligosaccharide (sLe x ), a natural ligand of selectin adhesion molecules. Reperfusion injury was assessed by established markers of injury. Apoptosis was determined by TUNEL and electron microscopy. Results: A third of the circulating platelets was rapidly sequestered in the liver after reperfusion. This was associated with increased graft injury. Single platelets were adherent to Sinusoidal lining without morphological or dynamic evidence of impairment of microcirculation. TUNEL staining revealed a 6-fold increase in the number of apoptotic SECs at 1 hour of reperfusion. No hepatocyte death or evidence of necrosis was detected up to 3 hours of reperfusion. Addition of sLe x inhibited adhesion and significantly reduced SEC apoptosis. Conclusions: Platelets cause SEC apoptosis upon reperfusion of liver grafts. Prevention of adhesion is protective. GASTROENTEROLOGY 2000;118:183-191
-
calpain inhibition prevents Sinusoidal Endothelial Cell apoptosis in the cold ischemic rat liver
Transplantation, 1999Co-Authors: David Sindram, Vivek Kohli, John F Madden, Pierrealain ClavienAbstract:Background. Cold preservation of the liver followed by reperfusion results in Sinusoidal Endothelial Cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. Methods. Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37°C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. Results. Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. Conclusion. Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation.
Nobuyuki Nakajima - One of the best experts on this subject based on the ideXlab platform.
-
vascular Endothelial growth factor secreted by replicating hepatocytes induces Sinusoidal Endothelial Cell proliferation during regeneration after partial hepatectomy in rats
Journal of Hepatology, 2001Co-Authors: Hiroaki Shimizu, Masaru Miyazaki, Yasuo Wakabayashi, Noboru Mitsuhashi, Atsushi Kato, Koji Nakagawa, Hiroyuki Yoshidome, Masaaki Kataoka, Nobuyuki NakajimaAbstract:Abstract Background : The aim of this study was to investigate regulatory mechanisms of Sinusoidal Endothelial Cell (SEC) proliferation after hepatectomy in rats. Methods : We investigated expressions of vascular Endothelial Cell growth factor (VEGF) and its receptors, flt-1 and KDR/flk-1, in regenerating liver after 70% hepatectomy. Proliferation of both hepatocytes and SECs was also monitored by evaluating the proliferating Cell nuclear antigen (PCNA) labeling index. Furthermore, VEGF production by cultured hepatocytes isolated at different times after hepatectomy was measured in vitro. Results : The expression of VEGF mRNA was increased markedly between 48 and 72 h after hepatectomy, and thereafter decreasing gradually. The immunohistochemical staining revealed that expression of VEGF started to increase 24 h after hepatectomy, with a peak at 72 h, and the majority of the VEGF-positive Cells were hepatocytes located in periportal areas. Meanwhile, expression of flt-1 and KDR/flk-1 was observed along the sinusoids even before hepatectomy, but was increased between 72 and 120 h. Furthermore, VEGF production by cultured hepatocytes isolated 72 h after hepatectomy was significantly increased. The PCNA labeling index of the SECs exhibited a delayed and slower regenerative response in comparison to the hepatocytes, reaching a peak at 72 h. Conclusions : These data strongly suggest that VEGF secreted by proliferating hepatocytes may represent an important stimulator of SEC proliferation.
-
obstructive jaundice impairs hepatic Sinusoidal Endothelial Cell function and renders liver susceptible to hepatic ischemia reperfusion
Journal of Hepatology, 2000Co-Authors: Hiroyuki Yoshidome, Masaru Miyazaki, Hiroaki Shimizu, Koji Nakagawa, Nobuyuki Nakajima, Hiroshi Ito, Satoshi Ambiru, Michael J Edwards, Alex B LentschAbstract:Abstract Background/Aims: Obstructive jaundice is associated with increased surgical morbidity and mortality. While parenchymal injury has been defined in obstructive jaundice, the pathogenesis of hepatic Sinusoidal Endothelial Cell injury in obstructive jaundice is unclear. The aims of this study were to investigate hepatic Sinusoidal Endothelial Cell injury in obstructive jaundice by determining serum hyaluronic acid levels, purine nucleoside phosphorylase/alanine aminotransferase ratios, and hyaluronic acid elimination rate, and also to determine whether hepatic parenchymal Cell injury in obstructive jaundice is induced more than in normal liver after hepatic ischemia/reperfusion. Methods: Male Wistar rats underwent ligation and division of the common bile duct (obstructive jaundice group) or sham operation (Sham group). Serum hyaluronic acid levels and purine nucleoside phosphorylase/alanine aminotransferase ratios in both groups were examined at intervals up to 21 days after surgery. Hepatic blood flow, permeability, neutrophil accumulation, and hyaloronic acid elimination rates in both groups were measured 14 days after surgery. Changes in serum hyaluronic acid and alanine aminotransferase concentrations were determined after 15 min of hepatic ischemia followed by reperfusion. Results: Serum hyaluronic acid levels remained elevated after bile duct ligation. Hepatic Sinusoidal Endothelial Cell swelling was observed by electron microscopy, and hepatic permeability was increased 14 days after bile duct ligation in association with neutrophil accumulation. Hepatic blood flow in obstructive jaundice remained unchanged, but hyaluronic acid elimination capacity was less than that in the Sham group. After hepatic reperfusion, the disappearance rate of serum hyaluronic acid in obstructive jaundice was lower, and serum alanine aminotransferase levels were higher than those in the Sham group. Conclusions: Our findings suggest that obstructive jaundice impairs Sinusoidal Endothelial Cells and that Sinusoidal Endothelial Cell damage in association with Sinusoidal deterioration during obstructive jaundice renders liver susceptible to ischemia/reperfusion relative to normal liver.
-
neutrophil mediated Sinusoidal Endothelial Cell injury after extensive hepatectomy in cholestatic rats
Hepatology, 1997Co-Authors: Masayuki Ohtsuka, Masaru Miyazaki, Yoichiro Kondo, Nobuyuki NakajimaAbstract:The aim of this study was to assess the hypothesis that hepatic failure after extensive hepatectomy in patients with obstructive jaundice (OJ) may be mediated by polymorphonuclear neutrophils (PMN). In the OJ group, rats underwent a partial hepatectomy of 78% after 2 weeks of cholestasis and subsequent external biliary drainage for 5 days. In the sham-operated control group, rats were partially hepatectomized 19 days after the sham surgery. The concentration of the serum cytokine-induced neutrophil chemoattractant (CINC), which is homologous with the growth-related oncogene (gro) product, a member of the human interleukin (IL)-8 family, and a major neutrophil chemotactic factor in rats, increased concomitantly with accumulation of PMNs in the hepatic sinusoids during cholestasis and subsequent external drainage. However, changes in the serum purine nucleoside phosphorylase (PNP)/alanine transaminase (ALT) ratio as a marker of Sinusoidal Endothelial Cell (SEC) injury showed no significant differences between the two groups. InterCellular adhesion molecule-1 (ICAM-1) expression on SECs was not affected by cholestasis and external drainage. After partial hepatectomy, the serum CINC concentration immediately elevated more prominently in the OJ group than in the sham-operated control group, and accumulation of PMNs in the sinusoids was more obvious and prolonged in the former. ICAM-1 expression was enhanced in both groups with a peak between 24 and 48 hours after partial hepatectomy. At this peak period, a significantly higher PNP/ALT ratio was observed in the OJ group. These results suggest that accumulation of PMNs in the Sinusoidal space and ICAM-1 expression on SECs might be closely associated with the development of SEC injury after extensive hepatectomy in cholestasis.