Regulation of hepatocyte glutathione content by hepatic sinusoidal cells activated with LPS: anatomical restrictions.
The liver is the main organ for the elimination of bacterial endotoxin involving Kupffer and parenchymal cells. This process is accompanied by the release of free radicals. Parenchymal cells possess especially high levels of glutathione, which make them a key point in the response to free radicals. Sinusoidal cells regulate hepatic function in a very important fashion through the release of cytokines and/or adhesion molecules. These facts suggest the importance of finding new in vitro experimental models representing an intermediate step towards in vivo models. The treatment with LPS of sinusoidal and parenchymal cell co-cultures on porous membranes provokes an intense reduction of parenchymal cell intracellular glutathione, which does not correspond to in vivo results. However, the addition of supernatants of LPS-treated sinusoidal cells to parenchymal cells renders increases in glutathione which agree better with in vivo results. We conclude that the regulation of liver hepatocyte glutathione content and NO release in the presence of LPS is strongly modulated by liver non parenchymal cells. The study of this phenomenon requires new in vitro models taking into account liver histophysiology and histopathology and anatomical restrictions in cell communication.
Department of Biology and Geology, ESCET, Universidad Rey Juan Carlos, Móstoles, Madrid, Spain. myriam.catala@urjc.es
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D000818:Animals; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004396:Coloring Agents / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014343:Trypan Blue / Q000378:metabolism
D004396:Coloring Agents; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D014343:Trypan Blue