Macrophage

Macrophages (abbr. Mø, from Ancient Greek μακρός macros " large" and ancient Greek φαγεῖν phagein "eat" ) are among the scavenger cells ( phagocytes ) and leukocytes (white blood cells), that belong to the cells of the immune system. They are used for removal of microorganisms by phagocytosis and provide phylogenetically ( phylogenetically ) which presumably oldest mediator of the innate immune defense dar. So macrophage -like cells in the fruit fly Drosophila and even in plants have been identified.

Development and occurrence

In the bone marrow monocytes to develop and migrate into the blood vessels, where they circulate throughout the body in the bloodstream. Come while in contact with infections, they are reinforced immigrate as neutrophils in the situation in the affected tissue. There they differentiate under the influence of cytokines and pathogen - substances in macrophages.

Depending on the stimulation they can take various forms: some greatly increase their cytoplasm and then are called epithelioid cells, because of their similarity to epithelial cells. Activated macrophages can also merge and form multinucleated giant cells to enclose larger foreign body for phagocytosis. To describe their localization in different tissues, them special names were given. So they called in the liver Kupffer cells in the lung alveolar macrophages, multinucleated osteoclasts and bone occurring in cartilage tissue chondroclasts, in the connective tissue histiocytes in the vitreous body of the eye hyalocytes and placenta Hofbauerzellen. Furthermore, macrophages found in breast milk, in which they serve the secretion of the enzyme lysozyme and immunostimulatory substances. Falsely microglia are often added to the macrophages counted. Microglia, however, do not develop in the bone marrow, such as macrophages, but originate in the prenatal period in the yolk sac of the embryo.

The term can also be done after the ingested material, then they are called, for example lipophages ( fat, such as " foam cells " in atherosclerotic plaques or fat necrosis ), Muziphagen ( schleimhaltig, such as salivary gland cysts ) or siderophages ( iron or hämosiderinhaltig, eg after bleeding or as "heart failure cells " in the lungs).

Function

Exogenous proteins or glycoproteins, such as on the surfaces of viruses and bacteria can be detected in tissue macrophages. In a process called phagocytosis, the microorganisms are added or active " bathed " and partially crushed intracellularly. At the same chemoattractants ( chemokines ) are released by this kind of " activated" macrophages and neutrophils that recruit other cells of its kind from the blood stream. Released cytokines at the same time provide for a local inflammation. The components of the previously recorded agent are then transported to the cell surface of macrophages and connected thereto by an MHC - II molecule.

Antigen presentation allows the activation of cells of the acquired immune response (T -helper cells). These in turn give now to the macrophages back a signal to the destruction of previously recorded pathogens. In contrast to dendritic cells, activated macrophages are limited able to activate naive (ie not in contact with an antigen Come ) T cells. Macrophages (especially those in secondary lymphoid organs) but contribute to the fact that T cells proliferate and differentiate strong " acting " in effector T cells and memory T cells. In addition to this activation of the acquired immune system eliminate macrophages also aged, destroyed, and apoptotic body's own cells. After successfully fighting infection macrophages are involved in the healing process by promoting scar formation ( granulation tissue ) and the formation of new blood vessels ( angiogenesis).

Macrophages can also be directly involved in the function of an organ. In the connective tissue of the testis, for example, to secrete 25 -hydroxy- cholesterol, a substance which is taken up by neighboring cells and Leydig there is used in the synthesis of testosterone. In case of inflammation of the testis, macrophages take their immunological task here and no longer available for the support of testosterone education. This leads to infertility.

Involvement in disease symptoms

In the case of tuberculosis taking macrophages according to their function the pathogen (usually Mycobacterium tuberculosis ) on. However, unlike other bacteria, the tubercle bacilli are able to survive inside macrophages due to the waxy nature of their cell wall. However, more monocytes are recruited from the blood, which transform into epithelioid cells and assemble. These are noted for their cats tongue-like nucleus macrophage descendants form a protective wall, in the center of the affected cells die. Enclosed by the epithelioid cells, structures of up to 1 mm in diameter is referred to as granuloma. The epithelioid cells can also fuse to form multinucleated Langhans giant cells, which are not to be confused with the Langerhans cells of the epidermis.

In dyslipidemia, obesity and diseases such as Niemann- Pick's disease or Alport syndrome macrophages can accommodate an excess of lipids and are then called " foam cells ". In the bloodstream form of this plays a role in the pathogenesis of atherosclerosis. In patients with heart disease may lead to a congestion in the lungs, which there is an accumulation of hemosiderin result. The local alveolar macrophages take on these iron -protein complex. These cells and their " cargo " are detectable in corresponding patient coughed in secretion of the respiratory mucosa. You can then also serve as diagnostic tools, which these macrophages, the term " heart failure cells " earned. Another special form of connective tissue macrophages are the " Anitschkow cells " that are involved in the formation of the rheumatic granuloma. This structure is also referred to as Aschoff nodules.

Discovery history

Based on Rudolf Virchow's proposal described Kranid Slavjanski 1863 for the first time that he, cells found in the alveoli of rabbits in their windpipe before he dribbled a cinnabar solution, " which had the character of white blood cells and sometimes also contained cinnabar ." Contrary to previous theories, he concluded from his experiments that these cells were not entstammend be seen as a " metamorphosed alveolar epithelium ", ie the lung mucosa. It lies " on hand to accept them as white blood cells which migrate out of the vessels ." According to present knowledge, thus he not only described the first " devouring " alveolar macrophages, but also their ability to migrate from the blood vasculature in organs.

Only Ilya Metchnikoff described in 1880 the principle of phagocytosis. Based on his study of phagocytic cells in starfish he coined the term " macrophage " and recognized its importance for the immune system. For these and other achievements in the description of the cellular immune defense Metchnikoff received together with Paul Ehrlich in 1908 the Nobel Prize for physiology and medicine.

In the first half of the 20th century, the function of the "fixed" tissue macrophages ( histiocytes ) described increased. On this basis, defined Ludwig Aschoff and other scientists, the principle of the reticuloendothelial system (RES ), which has been extended in the late 1960s under the name of mononuclear - phagozytierendes system.

Compared with other cells proved in subsequent years, the study of the cell biology of macrophages as difficult. It was not until the mid-1980s new insights into the importance of macrophages were obtained: Thus was discovered by macrophages after LPS contact one of them produced and previously unknown cytokine, tumor necrosis factor to also by the discovery of macrophage - specific growth factors such as M -CSF this time, new insight was gained into the cell differentiation of monocytes into macrophages.

In the 1990s, surface markers were increasingly used to locate subpopulations of macrophages in different tissues. In this way, existing definitions of tissue - specific macrophages could be strengthened.

Immunophenotype

Table is contained in the original with References for all items in PMID 22416241 (OA ).