Increased Serum Enzyme Levels Associated with Kupffer Cell Reduction with No Signs of Hepatic or Skeletal Muscle Injury (original) (raw)
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World journal of gastroenterology : WJG, 2006
Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by producing harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFbeta1 production, which lead...
Cytokinetic Analysis of the Expanding Kupffer-Cell Population Inrat Liver
Cell Proliferation, 1986
Zymosan stimulation in rats provides a useful model for studying the expansion of the Kupffer-cell population in liver, which represents the major population of tissue macrophages. This study, using tritiated-thymidine-labelling experiments, demonstrates that during population expansion at least 90% of the resident macrophages (Kupffer cells) develop proliferative activity. The mean duration of the cell cycle is estimated to be 52 hr, with an S phase of 7 hr. We have calculated that about 75% of population expansion results from local Kupffer-cell replication, whereas the remaining growth results from extrahepatic recruitment of macrophage precursors. These findings conflict with a concept of the mononuclear phagocyte system, which states that resident macrophages are (monocyte-derived) non-dividing end-cells. Macrophage populations in several organs are known to increase in size after stimulation by a variety of inflammatory agents (
Blood, 2007
Kupffer cells form a large intravascular macrophage bed in the liver sinusoids. The differentiation history and diversity of Kupffer cells is disputed; some studies argue that they are derived from blood monocytes, whereas others support a local origin from intrahepatic precursor cells. In the present study, we used both flow cytometry and immunohistochemistry to distinguish 2 subsets of Kupffer cells that were revealed in the context both of bone marrow transplantation and of orthotopic liver transplantation. One subset was radiosensitive and rapidly replaced from hematogenous precursors, whereas the other was relatively radioresistant and long-lived. Both were phagocytic but only the former population was recruited into inflammatory foci in response to CD8+ T-cell activation. We propose the name “sessile” for the radioresistant Kupffer cells that do not participate in immunoinflammatory reactions. However, we found no evidence that these sessile Kupffer cells arise from immature i...
Distinct development and functions of resident and recruited liver Kupffer cells/macrophages
Journal of Leukocyte Biology, 2013
Although mouse liver F4/80 ϩ Kupffer cells consist of cytokine-producing CD11b ϩ cells and phagocytic CD68 ϩ cells, an undefined CD11b Ϫ CD68 Ϫ subset (30%) also exists. We herein demonstrate a more fundamental classification by adding CD32 (Fc␥RII), which covers most liver F4/80 ϩ cells and the distinct functions of them. Among the F4/80 ϩ cells, 50%, 40%, and 30% of cells were CD32 ϩ , CD68 ϩ , and CD11b ϩ , respectively, and one-half of the CD68 ϩ cells coexpressed CD32. CD68 ϩ and CD32 ϩ cells, but not CD11b ϩ cells, expressed a phagocytosis-related CRIg. Gy (6) irradiation depleted liver CD11b ϩ cells and those in the spleen, bone marrow, and peripheral blood but not liver CD32/ CD68 ϩ cells. Transfer of bone marrow cells into the irradiated mice reconstituted liver CD11b ϩ cells. Conversely, clodronate pretreatment depleted only liver CD32/CD68 ϩ cells but not liver CD11b ϩ cells and peripheral blood or spleen CD11b ϩ monocytes/macrophages. Moreover, the CD32 ϩ cells might be precursors of CD68 ϩ cells, as a large proportion of CD32 ϩ cells expressed the c-kit (CD117), and CD34 and CD32 ϩ cells acquired CD68 immediately after bacteria administration. CD32/CD68 ϩ cells, but not CD11b ϩ cells, expressed resident macrophage-specific MerTK and CD64 (Fc␥RI). Challenge with Staphylococcus aureus or liver metastatic EL-4 tumor cells indicated that the CD68 ϩ subset is engaged in systemic bactericidal activity, whereas the CD11b ϩ subset is pivotal for liver antitumor immunity. Human liver CD14 ϩ Kupffer cells could also be classified into three similar subsets. These results suggest that liver CD68 ϩ Kupffer cells and CD11b ϩ Kupffer cells/macrophages are developmentally and functionally distinct subsets.
Frontiers in Immunology
Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as...
Inhibition of Kupffer Cells Reduced CXC Chemokine Production and Liver Injury
Journal of Surgical Research, 2001
Background. Cytokine production is a critical component of ischemia/reperfusion (IR) injury. In the liver, Kupffer cells produce cytokines and chemokines (i.e., cytokines with chemoattractant properties) that are important mediators in neutrophil recruitment and subsequent hepatocellular injury. Therefore, the role of Kupffer cells in chemokine production in hepatic IR injury was investigated.
REVIEW Role of the Kupffer Cell in Mediating Hepatic Toxicity and Carcinogenesis
2007
Kupffer cells are resident macrophages of the liver and play an important role in its normal physiology and homeostasis as well as participating in the acute and chronic responses of the liver to toxic compounds. Activation of Kupffer cells directly or indirectly by toxic agents results in the release of an array of inflammatory mediators, growth factors, and reactive oxygen
Infection and immunity, 1985
The potential of the resident murine Kupffer cell to be cytotoxic in extra- and intracellular killing systems in vitro was investigated. Kupffer cells exerted no spontaneous cytotoxicity but were readily susceptible to activation with lymphokines. Such activated Kupffer cells very efficiently killed extracellular P815 cells and intracellular Leishmania spp. parasites. Kupffer cells could be induced to proliferate in vitro under the influence of colony-stimulating factor (D.-M. Chen, H.-S. Lin, P. Stahl, and R. Stanley, Exp. Cell Res. 121:103-109, 1979). Kupffer cell-derived macrophages cultured in vitro were identical to their liver-derived progenitors in terms of macrophage-specific surface antigens and with respect to extra- and intracellular cytotoxicity. These results demonstrated that Kupffer cells have a strong self-renewing potential and that essential Kupffer cell properties like antigenic determinants and cytotoxic potential remained stable throughout the replicative proces...