Browsing by Subject "Kupffer cells"

Now showing 1 - 7 of 7
  • Thumbnail Image
    Publication
    Open Access
    Comparative in vivo and in vitro models to approach the cellular basis of endotoxic shock. The role of sinusoidal liver cells
    (Murcia : F. Hernández, 1996) Pagani, R.; Portolés, M.T.; Arahuetes, Rosa María; Ainaga, M.J.; Machín, Celia; Rúa, Carmen
    During endotoxic shock, the liver exerts a lipopolysaccharide (LPS) clearance function with the participation of both parenchymal and sinusoidal cells. Liver damage could be caused by LPS direct action, hypoxia and/or inflammatory mediators released by Kupffer cells. The aim of this study is to establish an experimental model that could allow us to understand the direct E. coli O1 1 l:B4 LPS action on sinusoidal cells. A comparative study was carried out, in vivo and in vitro, using either a rat reversible endotoxic shock model or sinusoidal cell cultures. The LPS was found to induce important and similar morphological alterations both in vivo and in vitro, specially in Kupffer cells. These cells present mitochondrial damage, nuclear membrane swelling, and increased number of phagosomes, including lamellar bodies. An immunocolloidal gold technique shows, in vitro, the LPS mainly located on Kupffer cell membrane and in phagosomes. The LPS binding to membrane, as a primary step of Kupffer cell activation, increases the phagocytosis. This effect could be related to a decrease of fluidity on the externa1 membrane portion.
  • Thumbnail Image
    Publication
    Open Access
    Expression and induction of anaphylatoxin C5a receptors in the rat liver
    (Murcia : F. Hernández, 2003) Schlaf, G.; Schmitz, M.; Rothermel, E.; Jungermann, K.; Schieferdecker, H.L.; Götze, O.
    The C5a-anaphylatoxin which is generated by limited proteolysis upon activation of the fifth component of complement may be induced by the classical, the alternative or the lectin pathway. C5a has been shown, under normal conditions, to induce the release of prostanoids from Kupffer cells (KC) and hepatic stellate cells (HSC) and thereby indirectly to increase glucose output from hepatocytes (HC). A direct action of C5a on HC would require the expression of the specific C5a receptor (C5aR). In studies using quantitative RT-PCR it was shown that non-stimulated HC lack C5aR, in contrast to KC, HSC and sinusoidal endothelial cells (SEC) all of which contained mRNA for the C5aR in decreasing amounts. FACS analyses, immunohisto- and immunocytochemistry as well as functional analyses confirmed the results of the RT-PCR assays. Under inflammatory situations the C5aR was found to be upregulated in various organs and tissues which included the liver. Interleukin-6 (IL-6) as a main inflammatory mediator in the liver induced a de novo expression of functional C5aR in HC in-vitro and invivo. In contrast, LPS failed to induce C5aR directly in cultured HC in-vitro but induced C5aR in HC in vivo and in co-cultures of HC and KC which release IL-6 upon stimulation with LPS. So far, the only known effector function of C5a on HSC was the induction of prostanoid release. In an approach to reveal new functions of C5aR in HSC, the cells responsible for liver fibrosis, it could be shown that C5a upregulated fibronectin-specific mRNA five-fold whereas entactin, collagen IV and the structure protein smooth muscle actin were not affected. In addition, C5a did not upregulate specific mRNA for the profibrotic cytokine TGF-ß1 in either isolated KC or HSC. Thus, C5a alone appears to have only a limited role in the induction of liver fibrosis.
  • Thumbnail Image
    Publication
    Open Access
    Immunodetection of aldose reductase in normal and diseased human liver
    (Murcia : F. Hernández, 2005) Brown, K.E.; Broadhurst, K.A.; Mathahs, M.M.; Kladney, R.D.; Fimmel, C.J.; Srivastava,S.K.; Brunt, E.M.
    Aldose reductase is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway that is implicated in the complications of diabetes. Aldose reductase appears to be involved in a variety of disease states other than diabetes, presumably due to its ability to catalyze the reduction of a broad spectrum of aldehydes, including some cytotoxic products of lipid peroxidation. Although the data regarding expression of aldose reductase in normal liver are conflicting, prior studies have suggested that the enzyme may be induced in diseased liver. The goal of these studies was to characterize expression of aldose reductase in normal and diseased human liver, using RT-PCR, Western analysis and immunohistochemistry. Aldose reductase transcripts and protein were detected at low levels in control human livers. In contrast, levels of aldose reductase mRNA and protein were increased in chronically diseased human livers. Immunohistochemistry demonstrated localization of aldose reductase in sinusoidal lining cells; dual immunofluorescence confocal microscopy with the macrophage marker, CD68, confirmed that the aldose reductase-positive sinusoidal lining cells were Kupffer cells. Abundant aldose reductase-positive, CD68- positive cells were present in the fibrous septa of cirrhotic livers, accounting for the increase in Immunostaining of human lung, spleen and lymph node revealed that macrophages in those tissues also express aldose reductase. These data are the first to demonstrate that aldose reductase is expressed by human macrophages in various tissues and suggest that this enzyme may play a role in immune or inflammatory processes.
  • Thumbnail Image
    Publication
    Open Access
    Kupffer cells and PlMs in acute experimental African Swine Fever
    (Murcia : F. Hernández, 1992) Carrasco, L.; Fernández, A.; Gómez-Villamandos, J. C.; Mozos, E.; Méndez, A.; Jover, A.
    An ultrastructural study of Kupffer cells and pulmonary intravascular macrophages (PIMs) of healthy and African Swine Fever (ASF)-infected pigs was carried out. A vascular perfusion method was performed in order to obtain an optimal intravascular morphology and tissue fixation. The infection developed acute ASF lesions in both organs. Both Kupffer cells and PIMs were studied at different stages of infection. The differences observed in both macrophagic cells from uninfected and infected tissues are shown and discussed.
  • Thumbnail Image
    Publication
    Open Access
    Liver gender dimorphism - insights from quantitative morphology
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Marcos, Ricardo; Correia Gomes, Carla; Miranda, Helena; Carneiro, Fatima
    It was shown recently that many genes are differentially expressed in the liver of males and females, thus strengthening the concept of liver gender dimorphism. This dimorphism exists in many pathological scenarios, from regeneration to fibrosis, which has led to the development of gender hepatology. Nevertheless, it is still unknown if gender dimorphism occurs in the structure of the normal liver. In recent years, it has been shown that, compared with male, the female rat liver bears less fibrotic tissue, more Kupffer cells (per volume unit) and has higher hepatocellularity, including binucleated hepatocytes (per volume unit). Our hypothesis is that the human liver also hides a gender dimorphic pattern. Baseline differences in fibrotic tissue would contribute to explain severe liver fibrosis in men. As to the disparity of Kupffer cells, this would clarify the stronger response to post-surgery infections in women, and it could be equated when appraising the higher susceptibility to alcohol. Regarding differences in hepatocytes, they not only justify existing differences in some liver parameters (e.g., transaminases and bilirubin), but they could also account for the higher regenerative potential of the female liver. The structural dimorphism in the human liver would sustain the concept of gender hepatology and, eventually, should be considered in the context of liver transplantation.
  • Thumbnail Image
    Publication
    Open Access
    Regulation of hepatocyte glutathione content by hepatic sinusoidal cells activated with LPS: anatomical restrictions
    (Murcia : F. Hernández, 2009) Catalá, Myrian; Pagani, Raffaella; Portolés, M.Teresa
    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.
  • Thumbnail Image
    Publication
    Open Access
    Yolkin tempers inflammatory mediator release and liver pathology in experimental endotoxemia in mice
    (2026) Jolanta Artym; Maja Kocięba; Ewa Zaczyńska; Kaleta-Kuratewicz; Jan P. Madej; Piotr Kuropka; Aleksandra Zambrowicz; Łukasz Bobak; Michał Zimecki; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Yolkin is an egg yolk-derived protein with immunoregulatory properties. In this work, yolkin was evaluated as a protective agent in endotoxemic BALB/c mice. The mice were pretreated with yolkin either orally in drinking water or intraperitoneally (i.p.) before i.p. injection of E. coli lipopolysaccharide (LPS). Circulating blood leukocyte number, blood cell composition, serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and haptoglobin, as well as histological changes in the spleen and the liver, were examined. Yolkin differentially regulated the values of these parameters, depending on the administration protocol; however, the serum levels of TNF-α and IL-6 were generally decreased, and the level of haptoglobin, an acute-phase protein, was elevated. The pretreatment of mice with yolkin led to improved histological architecture in the investigated organs of endotoxemic mice, particularly in the liver, where yolkin diminished an increased level of vascular permeability and reversed a decreased number of Kupffer cells. These changes were independent of the route of yolkin administration. In conclusion, yolkin proved effective in the amelioration of pathogenic consequences of LPS administration and may be considered a potential protective measure for patients at risk of endotoxemia. Histol Histopathol