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 on Kupffer Cell
1. What are Kupffer cells and where are they found in the body?
Kupffer cells are specialized macrophages that are permanently located in the liver. They reside within the liver's small blood vessels, known as sinusoids. This strategic position allows them to constantly monitor blood that has come from the digestive system, making them a vital part of the body's immune defence system.
2. What is the main function of Kupffer cells?
The primary function of Kupffer cells is phagocytosis, which means they act as the liver's 'cleaning crew'. Their key roles include:
- Engulfing and destroying pathogens like bacteria and viruses that enter the bloodstream from the intestine.
- Removing old, damaged, or dead red blood cells from circulation.
- Clearing away cellular debris and certain toxic materials.
- Initiating an immune response by releasing chemical messengers to alert other immune cells.
3. What is the difference between a Kupffer cell and a typical macrophage?
While all Kupffer cells are macrophages, not all macrophages are Kupffer cells. The main difference is that Kupffer cells are fixed or sessile, meaning they are resident cells that do not leave the liver sinusoids. In contrast, other macrophages, like monocytes in the blood, are motile and can travel to different parts of the body to fight infection. Kupffer cells are uniquely adapted to filter the large volume of blood passing through the liver.
4. How do Kupffer cells originate?
Kupffer cells have a dual origin. Most are derived from embryonic precursors that populate the liver during fetal development and are maintained through self-renewal. However, they can also be replenished by bone marrow-derived monocytes. These monocytes travel through the blood, enter the liver sinusoids, and differentiate into Kupffer cells, particularly in response to liver injury or inflammation.
5. What would happen to the body if the liver had no Kupffer cells?
Without Kupffer cells, the body's defence against gut-derived pathogens would be severely weakened. This could lead to:
- A higher risk of systemic infections (sepsis), as bacteria could pass from the intestine into the general bloodstream unchecked.
- Accumulation of harmful substances and cellular debris in the blood.
- An impaired immune response within the liver, making it more susceptible to damage and disease.
6. Can Kupffer cells ever be harmful to the liver?
Yes, in certain conditions, Kupffer cells can contribute to liver damage. In chronic diseases like alcoholic liver disease or non-alcoholic fatty liver disease (NAFLD), Kupffer cells can become persistently over-activated. This leads to the excessive release of inflammatory molecules that damage healthy liver cells (hepatocytes), promoting inflammation and the development of scar tissue (fibrosis), which can progress to cirrhosis.
