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  • br Vascular cells and the peribiliary vascular plexus

    2019-04-19


    Vascular cells and the peribiliary vascular plexus The liver is a highly vascularized organ that receives dual blood supplies from the hepatic portal vein (HPV) and hepatic GSK1120212 (Fig. 1). The HPV delivers approximately 75% of the total blood supply that the liver receives and carries from the spleen, gastrointestinal (GI), tract organs (i.e. stomach and small intestine), and other GI tract-associated organs. Hepatic arteries supply arterial blood accounting for the remaining 25% of blood received by the liver. Oxygen is brought in by both sources, each providing about half of the total amount of oxygen that the liver requires. Once blood enters the liver, it eventually flows through the liver sinusoids and empties into the central vein of each lobule. These central veins combine into the hepatic veins that exit the liver and drain into the inferior vena cava. The cells that line both blood and lymphatic vessels are called endothelial cells and form a type of simple squamous epithelium. Specifically, vascular endothelial cells form the endothelium that lines the entire circulatory system and come into direct contact with blood. They have unique functions within the cardiovascular system. In highly specialized areas such as the glomerulus in the kidney, they contribute to fluid filtration. The vascular endothelium also influences blood vessel tone by releasing nitric oxide and endothelin-1. In addition, vascular endothelial cells play a role in hemostasis and neutrophil recruitment as a part of the global immune response. A specific portion of the vasculature of the liver is responsible for supporting the needs of cholangiocytes that comprise the intrahepatic biliary tree. This structure is termed as the peribiliary plexus (PBP). The PBP stems from the hepatic artery and is located closely around intrahepatic bile ducts (Fig. 1). During development, the formation of bile ducts is closely associated with development of the hepatic artery, which is due to the fact that the GSK1120212 hepatic artery branches are in close proximity to the newly formed ductal plates. Biliary tree functions are closely linked to the PBP and can be seen when evaluating various models of cholestasis. Changes in the biliary tree (i.e. proliferation due to cholestasis) are associated with changes in the structure of the PBP. As cholangiocytes proliferate during cholestasis, they have an increase in metabolic demand. The PBP responds by proliferating and increasing in mass. There has also been evidence of a link between new blood vessel formation around bile ducts in response to chronic inflammatory liver diseases such as PBC and PSC. This new vessel growth plays an important role in remodeling the tissue after injury as well as delivering oxygen and other metabolic nutrients to hypoxic areas. These newly formed vessels can also provide pathways for the recruitment of inflammatory/immune response cells such as T lymphocytes.
    Mast cells MCs are myeloid cells derived from multipotent CD34-positive hematopoietic stem cells in the bone marrow. They are ubiquitous in nearly all tissues throughout vertebrates and can be found throughout the body, varying in concentration and size. MCs act as sentinel cells and maintain a close proximity in locations where they can rapidly respond to pathogens and antigens. MCs are found in numerous tissues and organs, epithelia, glands, the GI, smooth muscle, blood and lymphatic vessels, and nerves. The maturation of MCs is influenced by a diverse group of growth and differentiation factors in the niche where MCs reside. Stem cell factor (SCF) is a crucial signal secreted by tissues and other cells to promote MC migration, adhesion, and de novo proliferation, and can regulate MC development. In addition, MCs express c-Kit on their surface, which interacts with SCF and is a vital factor for MC migration and degranulation. It has been demonstrated that c-Kit mutations can result in tumor formation that may also involve MC activation.