Kupffer cell
Encyclopedia
Kupffer cells, also known as Browicz-Kupffer cells and stellate macrophages, are specialized macrophage
s located in the liver
lining the walls of the sinusoids that form part of the reticuloendothelial system
(RES) (also called mononuclear phagocyte system).
in 1876. The scientist called them "sternzellen" (star cells or stellate cells) but thought, falsely, that they were an integral part of the endothelium
of the liver blood vessels and that they originated from it. In 1898, after several years of research, Tadeusz Browicz
, a Polish scientist, identified them, correctly, as macrophage
s.
with the genesis of promonocytes and monoblasts into monocytes, and then on to peripheral blood monocyte
s, completing their differentiation into Kupffer cells.
is broken down by phagocytic action, and the hemoglobin
molecule is split. The globin chains are re-utilized, while the iron-containing portion or heme
is further broken down into iron, which is re-utilized, and bilirubin
, which is conjugated with 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.
, receptors on the Kupffer cell that internalize endotoxin
(lipopolysaccharide
or LPS). This activates the transcription of pro-inflammatory cytokine
s (Tumor necrosis factor-alpha or TNFα) and production of superoxide
s (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.
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s located in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
lining the walls of the sinusoids that form part of the reticuloendothelial system
Reticuloendothelial system
"Reticuloendothelial system" is an older term for the mononuclear phagocyte system. The mononuclear phagocyte system consists primarily of monocytes and macrophages. The spleen is the largest unit of the mononuclear phagocyte system. The monocyte is formed in the bone marrow and transported by the...
(RES) (also called mononuclear phagocyte system).
History
The cells were first observed by Karl Wilhelm von KupfferKarl Wilhelm von Kupffer
Karl Wilhelm von Kupffer was a Baltic German anatomist who discovered stellate macrophage cells that bear his name....
in 1876. The scientist called them "sternzellen" (star cells or stellate cells) but thought, falsely, that they were an integral part of the endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
of the liver blood vessels and that they originated from it. In 1898, after several years of research, Tadeusz Browicz
Tadeusz Browicz
Tadeusz Browicz was a Polish pathologist born in Lviv.He studied medicine in Kraków, earning his medical doctorate in 1873. Afterwards he remained at Kraków as an assistant to the pathologist Alfred Biesiadecki , and in 1875 received his habilitation...
, a Polish scientist, identified them, correctly, as macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s.
Development
Their development begins in the bone marrowBone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
with the genesis of promonocytes and monoblasts into monocytes, and then on to peripheral blood monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s, completing their differentiation into Kupffer cells.
Function
The red blood cellRed blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
is broken down by phagocytic action, and the hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
molecule is split. The globin chains are re-utilized, while the iron-containing portion or heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
is further broken down into iron, which is re-utilized, and bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, which is conjugated with glucuronic acid
Glucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
within hepatocytes and secreted into the bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...
.
Helmy et al. identified a receptor present in Kupffer cells, the complement receptor of the immunoglobulin family
Complement receptor of the immunoglobulin family
Complement receptor of the immunoglobulin family is a protein expressed in Kupffer cells....
(CRIg). Mice without CRIg could not clear complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
-coated pathogens. CRIg is conserved in mice and humans and is a critical component of the innate immune system.
Function in alcoholic liver disease
Kupffer cells activation are 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 CD14CD14
Cluster of differentiation 14 also known as CD14 is a human gene.The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms. Either it is anchored into the membrane by a glycosylphosphatidylinositol tail or it appears in a soluble form...
, receptors on the Kupffer cell that internalize endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...
(lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
or LPS). This activates the transcription of pro-inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s (Tumor necrosis factor-alpha or TNFα) and production of superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
s (a pro-oxidant). TNFα will then enter the stellate cell in the liver, leading to collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
synthesis and fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
. Fibrosis will eventually cause cirrhosis, or loss of function of the liver.