Бауыр макрофагтары және олардың қызметтері

Macrophages located in the liver

Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells comprise the largest population of tissue resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.

Kupffer cells can be found attached to sinusoidal endothelial cells in both the centrilobular and periportal regions of the hepatic lobules. Kupffer cell function and structures are specialized depending on their location. Periportal Kupffer cells tend to be larger and have more lysosomal enzyme and phagocytic activity, whereas centrilobular Kupffer cells create more superoxide radical. Kupffer cells are amoeboid in character, with surface features including microvilli, pseudopodia and lamellipodia, which project in every direction. The microvilli and pseudopodia play a role in the endocytosis of particles. The nucleus is indented and ovoid, and can be lobulated. Notable cytoplasmic elements include ribosomes, Golgi complexes, centrioles, microtubules and microfilaments. Kupffer cells also contain rough endoplasmic reticulum, a nuclear envelope, and annulate lamellae, all of which demonstrate peroxidase activity. Importantly, Kupffer cells express the SR AI/II scavenger receptor. This receptor is involved in recognising and binding the lipid A domain of lipopolysaccharide (LPS) and lipoteichoic acid. (Lipopolysaccharide (LPS) is a bacterial endotoxin which is found in the cell wall gram negative bacteria, whereas lipoteichoic acid is present in gram positive bacteria.) Because of this detection system, Kupffer cells play a critical role in initiating and mediating immune responses to bacterial infection of the liver. However, if resident Kupffer cell populations are depleted, monocytes derived from hematopoietic stem cells in the bone marrow and transported through blood circulation to the liver can also fully differentiate into true Kupffer cells. Unlike other tissue macrophages, which must be continually renewed by circulating monocytes, these monocyte derived Kupffer cells are capable of self renewal once a population is established. Development of mature Kupffer cells is regulated by numerous growth factors, with macrophage colony stimulating factor (CSF1) playing a key role. Cytokines involved in type 2 inflammation, such as IL 4, may also stimulate Kupffer cell proliferation. A time frame of 14 to 21 days for complete replenishment of Kupffer cell populations has been demonstrated in animal studies. Despite high monocyte influx and maturation rates, hepatic Kupffer cell populations are tightly maintained. Evidently, there is a high rate of turnover, with the average lifespan of a Kupffer cell estimated at 3.8 days. However, the ultimate fate of Kupffer cells in vivo is not yet fully understood.

Kupffer cells are incredibly plastic cells that have the capability to polarize specific activation states and can perform different functions in different microenvironments. M1 (classical activation) and M2 (alternative activation) designate the two extremes of macrophage polarization. M1 polarized Kupffer cells produce a large amount of pro inflammatory cytokines like TNF alpha. On the other hand, M2 polarized Kupffer cells produce a large quantity of anti inflammatory mediators, for example, IL 10.

The cells were first observed by Karl Wilhelm von Kupffer in 1876. The scientist called them "Sternzellen" (star cells or hepatic stellate cell) but thought, inaccurately, 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 identified them, correctly, as macrophages.