Liver endocytosis and Kupffer cells

Toth, Carol A.; Thomas, Dr.Peter

doi:10.1002/hep.1840160137

Cited by 114 publications

(59 citation statements)

References 157 publications

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“…The ability of endothelial liver cells to recognize and internalize apoptotic bodies has already been reported (Dini et al, 1995;Dini & Carla, 1998) and is in line with the capacity of the hepatic sinusoidal wall to interact with particulate materials (Steffan et al, 1986;Dini et al, 1993) and to operate as a protective barrier for the systemic circulation by removing potentially harmful materials carried by portal blood flow (i.e., bacterial endotoxins, microrganisms, immune complexes, tumor cells and other antigens) (Toth & Thomas, 1992). The possible involvement of hepatic carbohydrate receptors in apoptotic cell clearance is indirectly supported by i) the fact that the cell surface of dead cells expresses modified glycoproteins (in particular great amounts of galactose/N-acetyl-galactosamine/mannose residues); ii) that endothelial cells express on their cell surfaces the carbohydrate receptor systems; iii) that when the cell surface expression of these receptors on HSE is increased by LPS andILIß, phagocytosis of apoptotic PBL is markedly enhanced.…”

Section: Discussionsupporting

confidence: 68%

Phagocytosis of apoptotic cells: Liver recognition and molecular mechanisms

Dini

Carlà

Luca

et al. 1999

Italian Journal of Zoology

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The engulfment of cells undergoing apoptosis can be considered a specialized form of phagocytosis, playing a major role in general tissue homeostasis in physiological and pathological conditions. Although several systems of recognition on the surface of the phagocyte have been proposed to trigger or execute the apoptotic engulfment, the nature of the molecules involved and their molecular roles are still ill defined. In the present work, the molecular mechanisms of recognition of apoptotic cells by the hepatic sinusoidal wall were further investigated. The adhesion of apoptotic cells, i.e., lymphocytes isolated from human peripheral blood and a monocytic cell line U937, was studied in in vivo and in vitro experiments. Liver endothelial cells were able to recognize apoptotic lymphocytes in vivo as well as in vitro but failed, in the same conditions, to recognize apoptotic U937. A possible explanation could derive from the differences in the cell surface glycoconjugates of apoptotic lymphocytes and U937 visualized by using a panel of fluorescent lectins. By treating endothelial cells with lipopolisaccharides or interleukin ß1, that are known to increase the number of mannose-specific receptors on the endothelial cell surface, the adhesion of apoptotic cells doubled. Non apoptotic cells, irrespective of their source and type, normally escaped removal by sinusoidal liver cells.

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Section: Discussionsupporting

confidence: 68%

Phagocytosis of apoptotic cells: Liver recognition and molecular mechanisms

Dini

Carlà

Luca

et al. 1999

Italian Journal of Zoology

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“…This binding to endothelial cells may be explained by the ability of endothelial cells to bind matrix molecules (34), but also by the presence of other protein removal systems (35). pCVI-HSA displayed only minor binding to Kupffer cells, the hepatic cell type involved in the removal of large molecular weight molecules and foreign particles (33). Therefore, although the total distribution of pCVI-HSA to normal and fibrotic rat livers is almost identical, the intrahepatic distribution is completely different.…”

Section: Discussionmentioning

confidence: 98%

“…Attachment of cyclic peptides to the lysine groups of albumin might result in conformational changes of the albumin backbone due to electrostatic interactions between the carrier and the attached peptide moiety or the reaction conditions used for the coupling of cyclic peptides to HSA may cause a denaturation or refolding of the albumin molecule. This may lead to immunogenic responses or nonspecific removal by Kupffer cells or other macrophages in vivo (33). The identical CD spectra of pCVI- HSA and HSA, however, indicated that the conformation of the albumin molecule was not affected by the introduction of the 10 C*GRGDSPC* groups to albumin.…”

Section: Discussionmentioning

confidence: 99%

Successful Targeting to Rat Hepatic Stellate Cells Using Albumin Modified with Cyclic Peptides That Recognize the Collagen Type VI Receptor

Beljaars¹,

Molema²,

Schuppan³

et al. 2000

Journal of Biological Chemistry

134

105

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“…Whatever the domains involved, CEA could promote the development of liver metastases through homotypic or heterotypic adhesion between carcinomas cells themselves or between carcinoma cells and CEA trapped at the surface of Kupffer cells (Toth et al, 1992;Jessup et al, 1993a). Using ten human colon carcinoma cell lines, Tibbetts et al (1993) demonstrated that there is a connection between membrane CEA expression and the development of experimental liver metastases following i.s.…”

Section: Discussionmentioning

confidence: 99%

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

Leconte¹,

Garambois²,

Ychou³

et al. 1999

Br J Cancer

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Summary Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEAcDNA truncated at its 3′ end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 µg CEA per 10 6 cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 × 10 6 CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml -1 for tumours ranging from 100 to 1000 mm 3 ), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells.

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Liver endocytosis and Kupffer cells

Cited by 114 publications

References 157 publications

Phagocytosis of apoptotic cells: Liver recognition and molecular mechanisms

Phagocytosis of apoptotic cells: Liver recognition and molecular mechanisms

Successful Targeting to Rat Hepatic Stellate Cells Using Albumin Modified with Cyclic Peptides That Recognize the Collagen Type VI Receptor

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

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