Intrahepatic mast cells in chronic liver diseases*1

Farrell, D J; Hines, Julie E.; Walls, Andrew F.; Kelly, Peter; Bennett, Mark K.; Burt, Alastair D.

doi:10.1016/0270-9139(95)90627-4

Cited by 41 publications

(19 citation statements)

References 15 publications

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“…The density of mast cells is calculated at between 1.2 and 3.9 cells per square millimetre of human liver. Hepatic mast cells are mostly situated within connective tissue adjacent to the hepatic artery, hepatic vein and bile ducts of the portal tract [119]. Recent studies have shown the role of intrahepatic mast cells in different chronic liver diseases [119].…”

Section: Innate Immunity In Liver Inflammationmentioning

confidence: 99%

Innate Immune Cells in Liver Inflammation

Liaskou

Wilson

2012

Mediators of Inflammation

192

159

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Innate immune system is the first line of defence against invading pathogens that is critical for the overall survival of the host. Human liver is characterised by a dual blood supply, with 80% of blood entering through the portal vein carrying nutrients and bacterial endotoxin from the gastrointestinal tract. The liver is thus constantly exposed to antigenic loads. Therefore, pathogenic microorganism must be efficiently eliminated whilst harmless antigens derived from the gastrointestinal tract need to be tolerized in the liver. In order to achieve this, the liver innate immune system is equipped with multiple cellular components; monocytes, macrophages, granulocytes, natural killer cells, and dendritic cells which coordinate to exert tolerogenic environment at the same time detect, respond, and eliminate invading pathogens, infected or transformed self to mount immunity. This paper will discuss the innate immune cells that take part in human liver inflammation, and their roles in both resolution of inflammation and tissue repair.

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Section: Innate Immunity In Liver Inflammationmentioning

confidence: 99%

Innate Immune Cells in Liver Inflammation

Liaskou

Wilson

2012

Mediators of Inflammation

192

159

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“…Liver allograft rejection has been divided into hyperacute (humoral), acute (cellular), and chronic (ductopenic and/or arteriopathic) processes [10]. In recent years, many studies have suggested that hepatic mast cells are involved in chronic rejection [11], hepatic fibrogenesis [12], [13], [14], [15], and cholestatic liver diseases [13], [16]. Although mast cells are seen in normal liver surrounding the vessels and the bile ducts in the portal tracts, and to a much lesser extent, in the hepatic parenchyma [13], hepatic mast cells infiltrating portal tracts and surrounding damaged bile ducts have been focused as important effector cells in the pathogenesis of chronic rejection [11].…”

Section: Introductionmentioning

confidence: 99%

Immunological and Regenerative Aspects of Hepatic Mast Cells in Liver Allograft Rejection and Tolerance

et al. 2012

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The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow−derived mast cells (BMMCs) co-cultured with naïve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.

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“…Kupffer Cell numbers are approximately one-fourth the number of hepatocytes in the liver [42]. SEC numbers are approximately one-third the number of hepatocytes, and approximately one-eighth the number of mast cells exist compared to the number of hepatocytes [42, 44]. The initial number of hepatocytes was determined by an automated process of filling the region with hepatocytes in a 401 × 401 2D grid.…”

Section: Methodsmentioning

confidence: 99%

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

et al. 2016

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We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as “sepsis”. Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-α ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies.

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Intrahepatic mast cells in chronic liver diseases*1

Cited by 41 publications

References 15 publications

Innate Immune Cells in Liver Inflammation

Innate Immune Cells in Liver Inflammation

Immunological and Regenerative Aspects of Hepatic Mast Cells in Liver Allograft Rejection and Tolerance

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

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