What is Kupffer Cells?

A stellate shaped cells lining in the liver sinusoids are known as kupffer cells. So, these cells are also known as stellate macrophages.  This kupffer-browicz cells are specialized cells present in the liver within the lumen of the liver sinusoids. These cells are adhesive to their endothelial cells made up of blood vessel walls.  This kupffer cells will act as a phagocytic, which are capable to intake other cells of foreign particles.  The kupffer cells are found in the bone marrow and it stores hemosiderin. So, they are available for the production of hemoglobin. This takes responsible for oxygen -transportation in the red blood cells. The hemosiderin is an iron pigment, which is generated from the hemoglobin present in red blood cells.  

Kupffer cells also contain the wide range of tissue resident macrophages in the body.  Kupffer cells present in the liver will first come in contact with gut bacteria, bacterial endotoxins and microbial debris, which are transported to the liver from the gastrointestinal trach via the portal vein.  So, this is termed first immune cells in the liver.  Some alcoholic content, viral hepatitis, intrahepatic cholestasis, liver transplantation and liver fibrosis will make changes in kupgger cell functions. Kupffer cells are the part of  mononuclear phagocyte system. 

Structure of Kupffer Cells

The kupffer cells present in the liver are amoeboid shaped, they are attached to sinusoidal endothelial cells. The surface of kupffer cells contains pseudopodia, lamellipodia, and microvilli. They are projected in every direction. The pseudopodia and microvilli play an important role in endocytosis. The cytoplasm present inside the kupffer cells contains ribosomes, centrioles, microfilaments, Golgi apparatus, and microtubules. Kupffer cells contain a nucleus, which is indented, ovoid and they can be lobulated. The rough endoplasmic reticulum, annulate lamellae, and nuclear envelope are also present inside the kupffer cells and all contain peroxidase activity. The structure and kupffer cells function are depending on their location in the liver. But, the centrilobular and periportal regions of the liver are known houses of these cells. The kupffer cells present in the periportal region are comparatively larger and have more lysosomal enzyme and phagocytic activity.  Likewise, the kupffer cells from the centrilobular region have more superoxide radicals. Kupffer cells contain SR-AI/II scavenger receptor, which is involved in recognizing and binding the lipid A domain of lipopolysaccharide and lipoteichoic acid. Usually, lipopolysaccharide is a bacterial endotoxin present in the cell wall of gram-negative bacteria. Further, lipoteichoic acid is present in gram-positive bacteria. 

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Development of Kupffer Cells

The development of kupffer cells starts from the yolk sac of an individual, then they differentiate into fetal macrophages. When they are entering into the bloodstream, they will migrate to the fetal liver.  Further, they complete their development and turns to kupffer cells. 

The hepatic macrophages are of two types.  Kupffer cells will stay inside the liver, which was originated from the yolk sac-derived red bone marrow progenitor cells. The monocyte-derived macrophages are derived from the hematopoietic stem cells, which are located in the bone marrow. They are transported to the liver through blood circulation. Here, the monocyte-derived macrophages are immunogenic macrophages, which differentiate the influence of the microenvironment. Kupffer cells can self-sustain, so they can locally proliferate to attack the phagocytic cells. Monocytes present in the peripheral circulation have come from bone marrow’s precursor cells. The peripheral blood monocytes entering the liver can mature into phenotype characteristic of tissue macrophages.  The macrophages may differ depends on various growth factors.  The stimulating macrophage colony plays an important role in the development of kupffer cells. 

Kupffer Cells Function

The average life span of the kupffer cells is around 3 - 8 days. The primary kupffer cells function is to remove the foreign particles and debris, which enters the liver through the portal system. Usually,  Kupffer cells will take large particles through phagocytosis and smaller particles through pinocytosis. Kupffer cells will act as an innate response for the immune system. Important kupffer cells function is to defense against the cells attacking host cells. It also plays an important role in the metabolism of many compounds includes lipids, protein complexes, and small particles. Kupffer cells can also remove apoptotic cells from blood circulation. The count of kupffer cells usually remains constant in the liver. But they are regulated by apoptosis, as well as phagocytized by kupffer cells near to it. The Kupffer cells have a proliferative capacity, so they can regenerate by themselves.  This is completely different from monocyte-derived macrophages, which do not have proliferative potential. 

Kupffer cells are showing heterogeneous function, which completely depends on their location. For example, Liver lobules in zone 1 are much more active than their counterparts in zone 3. 

Likewise, the exposure to damage of cells in zone 1 has a higher probability than in zone 3. 

Kupffer cells can secrets TNF alpha, cytokines, oxygen radicals, cytokines, and proteases to perform phagocytosis.  Those are helpful for the development of the liver from injury. 

Kupffer cells will play a major role in clearing bacteria. Further, the red blood cells get broken down by phagocytic action. During this time, the hemoglobin molecule get splits into heme and globin.  Here, the globin is re-used and the iron-containing portion heme is further broken to form iron and re-used. Further, bilirubin is conjugated to glucuronic acid within hepatocytes and secretes from the bile. The receptor present in kupffer cells are identified by  Helmy et al. It is 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.

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FAQs (Frequently Asked Questions)

Q1. What is the Function of the Kupffer Cells in the Liver?

Ans: Kupffer cells occur in liver macrophages. It plays an important role in maintaining liver function. Under physiological conditions, kupffer cells will act as innate immune cells and protect the liver from various bacterial infections.  Kupffer cells present in the liver usually contain 80%–90% of all macrophages and 35% of non-parenchymal cells.  Also, kupffer cells will secrete inflammatory cytokines, oxygen radicals, TNF - alpha, and proteases. It is also performing phagocytosis. This helps them to recover from liver injury. 

Q2. Where Do Kupffer Cells Originate?

Ans: The liver contains four major cells, they are hepatic stellate cells, hepatocytes, liver sinusoidal endothelial cells, and kupffer cells. These cells will spatiotemporally cooperate to shape and maintain liver functions. Kupffer cells are found in the bone marrow. These bone marrow monocytes will enter the blood circulation and implant into the liver, where the bone marrow differentiate into fixed tissue macrophages.

Q3. What If the Liver Did Not Have Kupffer Cells?

Ans: Kupffer cells present in liver macrophages will play important role in maintaining liver function and acts as an innate immune system to protect the liver.  The absence or lower presence of kupffer cells in the liver can contribute to pathogen invasion, inflammation..etc.  Sometimes, if the kupffer cells are activated during the NAFLD/NASH liver disease, it may lead to an uncontrolled inflammatory condition in the liver.