Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors

McCourt, Peter; Smedsrød, Bård; Melkko, Jukka; Johansson, Staffan

doi:10.1002/hep.510300521

Cited by 128 publications

(143 citation statements)

References 49 publications

(86 reference statements)

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“…28 Endothelial cells lining bone marrow sinuses share some of these properties with hepatic endothelial cells. 27 In ultrastructural studies, Anton found that a single 300 mg/kg IP dose of CP injured bone marrow and hepatic endothelial cells in 2 mouse strains.…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

et al. 2002

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To determine whether disruption of the hepatic sinusoidal endothelium will facilitate engraftment of transplanted cells, we treated Fischer 344 (F344) rats lacking dipeptidyl peptidase IV (DPPIV) activity with cyclophosphamide (CP). Electron microscopy showed endothelial injury within 6 hours following CP, and, after 24 and 48 hours, the endothelium was disrupted in most hepatic sinusoids. CP did not affect Kupffer cell function. Similarly, CP had no obvious effects on hepatocytes. Intrasplenic transplantation of F344 rat hepatocytes followed by their localization with DPPIV histochemistry showed 3-to 5-fold increases in the number of transplanted cells in CP-treated animals. Transplanted cells integrated in the liver parenchyma more rapidly in CPtreated animals, and hybrid bile canaliculi developed even 1 day after cell transplantation, which was not observed in control animals. To demonstrate whether improved cell engraftment translated into superior liver repopulation, recipient animals were conditioned with retrorsine and two-thirds partial hepatectomy (PH), which induces transplanted cell proliferation. CP treatment of these animals before cell transplantation significantly increased the number and size of transplanted cell foci. In conclusion, disruption of the hepatic sinusoidal endothelium was associated with accelerated entry and integration of transplanted cells in the liver parenchyma. These results provide insights into hepatocyte engraftment in the liver and will help in optimizing liver-directed cell therapy. ( T ransplanted hepatocytes integrate in the liver, survive throughout the life of animals, and express genes normally. 1-3 However, several days are required for transplanted cells to integrate in the liver parenchyma. 4 Moreover, transplanted cells do not proliferate significantly in the normal adult liver, 3 although, when proliferation and/or survival of native and transplanted cells are dissociated, transplanted hepatocytes can repopulate the liver extensively. [5][6][7][8][9][10] The possibility of therapeutic liver repopulation has been tested in several animal models with liver failure, genetic diseases, and metabolic deficiency states. [11][12][13][14] The swiftness with which transplanted cells engraft could be critical for liver repopulation. After injection into the portal system, transplanted cells lodge in hepatic sinusoids because of differences in the dimensions of these cells and sinusoids. 15 This is associated with changes in native hepatocytes, such as gamma-glutamyl transpeptidase activation and disruption of gap junctions. 16 The sinusoidal endothelium is disrupted 16 to 20 hours after transplantation, which provides transplanted cells access to the space of Disse. 4 Transplanted cells then translocate into the liver plate, with reconstitution of gap junctions and bile canaliculi over 3 to 7 days. However, delays in cell engraftment affect transplanted cell proliferation. In rats subjected to two-thirds partial hepatectomy (PH), which induces hepatic DNA synthesis within ...

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Section: Discussionmentioning

confidence: 99%

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

et al. 2002

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“…The hyaluronan receptor shares functional properties with the scavenger receptor family (McCourt et al 1999).…”

Section: Disposal Of Waste Moleculesmentioning

confidence: 99%

Immune Functioning in Non lymphoid Organs: The Liver

Parker

Picut

2011

Toxicol Pathol

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The liver is the primary hematopoietic organ of the mammalian body during the fetal stage. The postnatal liver retains immunologically important functions and contains a substantial population of immunologically active cells, including T and B lymphocytes, Kupffer cells, liver-adapted natural killer (NK) cells (pit cells), natural killer cells expressing T cell receptor (NKT cells), stellate cells, and dendritic cells. The liver is the major site of production of the acute phase proteins that are associated with acute inflammatory reactions. Kupffer cells have an important role in the nonspecific phagocytosis that comprises a major component of the barrier to invasion of pathogenic organisms from the intestine. Hepatic NK and NKT cells are important in the nonspecific cell killing that is important in resistance to tumor cell invasion. The liver has a major role in deletion of activated T cells and induction of tolerance to ingested and self-antigens. Disposal of waste molecules generated through inflammatory, immunologic, or general homeostatic processes is accomplished via the action of specific endocytic receptors on sinusoidal endothelial cells of the liver. Age-related changes in sinusoids (pseudocapillarization), autophagy, and functions of various hepatic cell populations result in substantial alterations in many of these immunologically important functions.

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“…The uptake per cell population in the total liver was calculated based on the rat liver ratio KCs:LSECs:PCs=1:2.5:7.7 [33]. antibody [17,28]. LSEC preparations were between 95-98% pure.…”

Section: Hepatocellular Distributionmentioning

confidence: 99%

Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

Øie

Appa

Hilden

et al. 2011

Journal of Hepatology

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Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors

Cited by 128 publications

References 49 publications

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

Immune Functioning in Non lymphoid Organs: The Liver

Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

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