08/03/2014
Kupffer cell
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Kupffer cells, also known as Browicz-Kupffer cells and stellate macrophages, are specialized macrophages located in the liver lining the walls of the sinusoids that form part of the reticuloendothelial system (RES) (also called mononuclear phagocyte system).
Development
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Their development begins in the bone marrow with the genesis of promonocytes and monoblasts into monocytes, and then on to peripheral blood monocytes, completing their differentiation into Kupffer cells.
Function
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Red blood cells are broken down by phagocytic action, where the haemoglobin molecule is split. The globin chains are re-utilized, while the iron-containing portion, heme, is further broken down into iron, which is re-utilized, and bilirubin, which is conjugated to glucuronic acid within hepatocytes and secreted into the bile.
Helmy et al. identified a receptor present in Kupffer cells, the complement receptor of the immunoglobulin family (CRIg). Mice without CRIg could not clear complement system-coated pathogens. CRIg is conserved in mice and humans and is a critical component of the innate immune system.
Function in alcoholic liver disease
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Kupffer cell activation is responsible for early ethanol-induced liver injury, common in chronic alcoholics. Chronic alcoholism and liver injury deal with a two hit system. The second hit is characterized by an activation of the Toll-like receptor 4 (TLR4) and CD14, receptors on the Kupffer cell that internalize endotoxin (lipopolysaccharide or LPS). This activates the transcription of pro-inflammatory cytokines (Tumor necrosis factor-alpha or TNFα) and production of superoxides (a pro-oxidant). TNFα will then enter the stellate cell in the liver, leading to collagen synthesis and fibrosis. Fibrosis will eventually cause cirrhosis, or loss of function of the liver.
