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The mononuclear phagocyte system.

The mononuclear phagocyte system (MPS) has been defined as a family of cells comprising bone marrow progenitors, blood monocytes and tissue macrophages. Macrophages are a major cell population in most of the tissues in the body, and their numbers increase further in inflammation, wounding and malignancy. Their trophic roles for other cell types in development and homeostasis are becoming increasingly evident. The receptor for macrophage colony-stimulating factor (CSF-1R) is expressed in a large proportion of cells considered to be mononuclear phagocytes, including antigen-presenting dendritic cells, which can be considered a specialized adaptive state rather than a separate lineage. The unity of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, by the transdifferentiation and fusion of MPS cells with other cell types, and by evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. The concept of the MPS may have partly outlived its usefulness.

Animals↗

The mononuclear phagocyte system revisited.

The mononuclear phagocyte system (MPS) was defined as a family of cells comprising bone marrow progenitors, blood monocytes, and tissue macrophages. In this review, we briefly consider markers for cells of this lineage in the mouse, especially the F4/80 surface antigen and the receptor for macrophage colony-stimulating factor. The concept of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, the blurring of the boundaries between macrophages and other cells types arising from phenotypic plasticity and transdifferentiation, and evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. Nevertheless, there is a unity to cells of the MPS suggested by their location, morphology, and shared markers. We discuss the origins of macrophage heterogeneity and argue that macrophages and antigen-representing dendritic cells are closely related and part of the MPS.

Animals↗

[Correlation between the extrarenal renin-angiotensin system and the mononuclear phagocyte system].

Authors survey the cyto-biological effect of extra-renal renin-angiotensin system on the basis of literature data and of their own previous results. It is established that renin and angiotensins in extra-renal localisation take part mainly in inflammatory process. In this respect, one of the important target cell group of angiotensin system is the certain elements of mononuclear phagocyte system, on which angiotensin II has cytokine-like effect. Renin-angiotensins detected by authors in non-activated alveolar mono-phages and monocytes raise the possibility, that these cells also have independent, intra-cellular regulating renin-angiotensin.

Biological Factors↗

[Pathology of the phagocytic mononuclear system. Apropos of 4 cases].

Four patients, with disorders belonging to mononuclear phagocyte system diseases are described: a case of malignant histiocytosis; one of Weber-Christians disease and two siblings affected by familiar erythrophagocytic lymphohistiocytosis. An attempt is made to update classification of this group of diseases previously known as reticulosis, reticulohistiocytosis, reticuloendotheliosis, etcetera.

Child↗

[Immunohistochemistry of the human mononuclear phagocytic system].

Monocytes and macrophages comprising the so called mononuclear phagocyte system are characterized by an astonishing diversity with respect to morphology as well as function. Lysosomal acid hydrolases, specially the unspecific acid esterase (EC 3.1.1.6) have been widely used to characterize and recognize this cell system. It was the aim of this study to further clarify the heterogeneity of the mononuclear phagocyte system using acid hydrolases and related typical intracytoplasmic structures, the lysosomes, as biochemical as well as immunological markers. The following results were obtained: 1. Human blood monocytes and their macrophage derivatives are characterized by an extraordinary isoelectric focusing pattern of the unspecific acid esterase, which could not be observed in all other normal human blood cells. 2. The monocyte specific isoelectric focusing pattern of unspecific acid esterase is also observable under neoplastic conditions: The typical pattern can be recognized in monocytic leukemias as well as in the permanent monocytic cell line U-937. 3. The isoenzymes of monocytic acid esterase as well as lysosomes of stimulated U-937 cell line are cell specific antigens: Polyclonal antisera raised against these structures recognize physiological functional forms, pathologic reaction forms, as well as neoplastic variants of the mononuclear phagocyte system applying immunohistochemistry. 4. The broad reactivity spectrum of polyclonal antibodies raised against lysosomes can be subdivided in different reactivity patterns by monoclonal antibodies. With the latter reagents it could be shown that monocytes not only differentiate in phagocytes but also in two populations of immune accessory cells thus mirroring the bipolarity of immune response as shown by T and B lymphocytes. The established biochemical as well as immunohistochemical markers open the possibility to characterize the different neoplasias originating from the mononuclear phagocyte system. Furthermore, it is hoped that the morphological as well as immunohistochemical heterogeneity is also paralleled by special functions expressed by the recognized subcohorts.

Acetylesterase↗

Neoplasms of the mononuclear phagocyte system: criteria for diagnosis.

The Mononuclear Phagocyte System, including promonocytes, monocytes, and tissue histiocytes (macrophages), gives rise to moncytic leukaemias and histiocytoses. A classification of these neoplasms by their presumed cell of origin is proposed, and criteria for their diagnosis are given. Histopathological, cytochemical, immunological and ultrastructural features useful in distinguishing these disorders form other haematopoietic or lymphoid neoplasms are presented in detail. The resulting classification reflects our knowledge at this time; as techniques become available to define further functional subpopulations of mononuclear phagocytes, it is likely that this classification will become as diverse as that of lymphoid neoplasms.

Antigens, Neoplasm↗

Endocytosis by the mononuclear phagocyte system and autoimmune disease.

The mononuclear phagocyte system, formerly called the reticuloendothelial system, is an important element in basic immunology, cell biology, and clinical disease. Secretory products participate in inflammation and immunoregulation. Endocytosis mediated by specific receptors for immunoglobulin and complement or by other opsonins is important in removal of damaged self or foreign particles. The ability to assess receptor-specific endocytosis has led to the recognition of Fc-receptor dysfunction in certain autoimmune diseases. This defect in membrane receptor function, whether inherited or acquired, may be important in the pathogenesis of these diseases.

Animals↗

Increased susceptibility of malaria-infected variant erythrocytes to the mononuclear phagocyte system.

The interactions of the mononuclear phagocyte system with Plasmodium falciparum-infected genetically variant erythrocytes may result in a significant protection for the host. Infected hemoglobin (Hb) EE and Hb EA erythrocytes are more susceptible to phagocytosis by monocytes than are infected Hb AA erythrocytes. The increased susceptibility to phagocytosis of infected erythrocytes was also found for a number of genetic variants involving the alpha-globin chain, namely, alpha-thal 1 trait (--/alpha alpha), alpha-thal 2 trait (-alpha/alpha alpha), Hb H (--/-alpha), Hb H/Hb Constant Spring (CS) (--/alpha CS alpha), Hb CS trait, and homozygous Hb CS erythrocytes. In addition, oxidative damage from hydrogen peroxide, produced in simulation of macrophages, led to much more effective killing of parasites in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes than in normal ones. Parasites infecting Hb H/Hb CS also showed an enhanced sensitivity to hydrogen peroxide.

Animals↗

[Changes in the rate of protein synthesis in parenchymatous liver cells during stimulation of the mononuclear phagocyte system].

In vivo stimulation of mononuclear phagocyte system (MPS) by zymosan, dextrane sulfate, and prodigiosan caused almost a two-fold increase in hepatic protein synthesis. The rate of 14C-leucine incorporation increased both into total and soluble proteins. To define the cellular locus of these changes, preparations of hepatic parenchymal and nonparenchymal cells were obtained from the control and LPS-stimulated rats. The results indicate that the treatment of rats with prodigiosan stimulate protein synthesis in hepatocytes. No effect on protein synthesis of non-parenchymal cells was observed. Stimulation of MPS also caused a significant increase in 14C-leucine incorporation into serum lipoproteins. The results suggest that MPS may be involved in regulation of protein synthesis in hepatic parenchymal cells.

Animals↗

Autologous immune complex nephritis in rats. Influence of modification of mononuclear phagocyte system function.

These studies were designed to determine the effect of modification of mononuclear phagocyte system function on a chronic immune complex disease. Autologous immune complex nephritis in rats (Heymann nephritis) was induced by immunization with renal tubular epithelial antigen (Fx1A). The mononuclear phagocyte system was impaired by splenectomy and stimulated by weekly intraperitoneal injections of zymosan. Serial determinations included 24-hour urinary protein excretion, serum antibody titers, C3, circulating immune complexes, creatinine, and creatinine clearance. Renal tissue was obtained at 21, 42, and 56 days after immunization to evaluate by immunofluorescence the amount of antigen and IgG deposited. Splenectomized rats with Heymann nephritis had significantly greater amounts of glomerular Fx1A antigen and IgG deposits at each time studied than did rats without modification of mononuclear phagocyte system function. Zymosan-treated rats had very few glomerular deposits. In the splenectomized rats, the creatinine clearance was depressed by 50%. All animals had normal levels of C3 and identical antibody titers. In an independent assessment of mononuclear phagocyte system function, plasma clearance of Fx1A was enhanced in zymosan-treated animals and depressed in splenectomized animals. These modifications of mononuclear phagocyte system function were associated with changes in the amount of glomerular deposits of IgG and the clinical course of membranous nephropathy in this animal model. Application of methods for stimulation of mononuclear phagocyte system function may have therapeutic efficacy in the future treatment of human membranous nephropathy.

Animals↗

[Sturcture and function of the mononuclear phagocytic system (MPS) in chronic rhinosinusitis. A light and electron microscopic investigation (author's transl)].

Neither the concept of the Reticulo-Endothelial-System (RES) Aschoff's (1924) nor that of the Reticulo-Histiocyte-System (RHS) provides a satisfactory framework into which the present knowledge of the phagocytic mononuclear cells can be fitted. Current knowledge concerning morphology, histochemistry (peroxydase and esterase activity), immunology (specific surface antigens, receptors on the cell membranes), function (immune phagocytosis, pinocytosis), kinetics (3H-thymidine labelling) and culture makes it possible to place all highly phagocytic mononuclear cells and their precursors in one system, which is called the Mononuclear-Phagocytic-System (MPS) (Langevoort, Cohn, Hirsch, Humphrey, Spector, van Furth, 1969). Kinetic studies with labelled cells have shown, that mononuclear phagocytes originate from precursor cells in the bone marrow (stem cell leads to monoblasts leads to promonocytes), than are circulating in the peripheral blood as monocytes and are transformed to tissue macrophages entering tissues. The MPS comprises following cells in following organs: connective tissue (histiocytes resp. macrophages); liver (Kupffer-cells); lung (alveolar macrophages); lymph nodes (free and fixed macrophages); bone marrow (macrophages); serous cavities (pleural and peritoneal macrophages); bone tissue (osteoclasts?); nervous system (microglial cells) (SEE Table 1). The reticular cells, endothelial cells and fibroblasts (fibrocytes) can therefore not be included in the MPS. Besides differences in morphology, histochemistry and function, they derive from mesenchymal cells and not from the bone marrow as the MPS. The present investigation demonstrates the structure and significance of the MPS in various kinds of chronic-specific and non-specific rhinosinusitis. On semithin sections two kinds of macrophages can be distinguished light-microscopically: 1. Larger macrophages with many phagosomes (storage cells) (Fig. 1A), which can exhibit sometimes a ring-shape on sections embracing greater parts of the interstitium (Fig. 1B). Such forms are mainly found in chronic (maxillary) sinusitis and are interpretated as "scavenger" macrophages. 2. The second type consists of smaller macrophages with extremely ruffling of the cell surface, which is interpretated as an expression of highly (specific?) stimulated states. These later macrophages can be seen mainly in edematous nasal polyps, which might be caused by allergic reactions of the anaphylactic type. The fine structure of the phagocytes is to some extent dependent on the actual development and functional state: there are "immature" macrophages, which are practically indistinguishable from blood monocytes (Fig. 2A); some of them can be stimulated and can therefore show many surface foldings and projections (Fig. 2B). The "mature" macrophage shows a well developed Golgi-area and many secondary lysosomes (Fig. 3). The storage type of the macrophages, which can predominate in some cases of chronic maxillary sinusitis, is characterized by many electron-lucent vacuoles (Fig. 4)...

Chronic Disease↗

[Effect of doxorubicin on the functional state of the mononuclear phagocyte system].

The response of the system of mononuclear phagocytes (SMP) to doxorubicin, an antitumor antibiotic, most widely used in oncological care, was studied. It was shown that a single intraperitoneal administration of doxorubicin to CBA mice in the maximum tolerance doses induced suppression of absorptive SMP capacity and increased IL-I secretion by the bone marrow and peritoneal macrophages both in the stimulated and spontaneous tests in early periods after cytostatic administration. There was a significant rise in the ability of SMP bone marrow elements to respond to the macrophage activating factor, as well as an increase in the cytotoxic activity of bone marrow and peritoneal macrophages.

Animals↗

[Mononuclear phagocyte system. Morphology and function of the principal constituting cells].

Histo-monocytes are cells playing an important role in host defense reaction and purification of the organism. These cells belong to a new system of highly phagocytic mononuclear cells termed "mononuclear phagocyte system". This system includes the promonocytes and their precursors in the bone marrow, the monocytes in the peripheral blood and the different types of histiocytes and macrophages particularly Kupffer cells. Histiocytes can also transform into epithelioid cells and giant cells. The inclusion of all these cells in this system is based on similarities in the morphology, function, origin and kinetics of the phagocytes. The most important morphologic characteristics of these cells are described. It is also shown that the mononuclear phagocytic system is a secretory system. The different types of products are described. Recently, so-called accessory cells of the immunity were described, comprising dendritic reticular cells from the follicles and interdigitating reticular cells from the deep cortical zone of the lymph node. Those cells belong both probably to the system. The cells of this system are engaged in the clearance of multiple organs, in the inflammatory process, in the immune response and in the immune surveillance against tumor.

Animals↗

[Reproduction of experimental leprous infection in mice with a preliminary modelling of failure of the mononuclear phagocyte system].

CBA mice with induced insufficiency of mononuclear phagocyte system (MNPS) were inoculated intraplantar with M. leprae in a dose of 1 X 10(4). A significantly accelerated multiplication of M. leprae was noted in the sites of inoculation with the development of a generalized infections process and appearance in 6 months after inoculation of lepromatous structures in spleen, liver and other internal organs as compared with the animals with unchanged MNPS. The data obtained suggest that insufficiency in macrophage component of cell-mediated immunity might underline the sensibility to leprosy infection.

Animals↗

Evaluation of aggregated IgG in mice as an Fc receptor specific probe of the hepatic mononuclear phagocyte system.

In experimental models of immune complex diseases the hepatic mononuclear phagocyte system removes circulating immune complexes (CIC) by interaction with Fc receptors, and the spleen has a relatively insignificant role in this function. We have used heat-aggregated human IgG (AHGG) to detect altered hepatic mononuclear phagocyte system activity in an acute immune complex model in mice in order to evaluate its suitability for possible use in humans. Immune complexes inhibited the clearance of AHGG, as a function of the dose and of the time after injection of complexes. The delayed clearance resulted from decreased hepatic uptake of the AHGG. Alterations in the comparatively small splenic uptake of AHGG did not correlate with changes in the clearance or the hepatic uptake that were produced by the complexes. Studies with Rose Bengal showed that the complexes caused a small but definite decrease in hepatic blood flow. Immune complexes also inhibited the clearance and hepatic uptake of aggregated mouse albumin and aggregated ovalbumin. The aggregated albumins, however, were cleared very rapidly, indicating high extraction ratios, so their clearance was more affected by the decreased blood flow than the clearance of AHGG. We conclude that a small dose of AHGG is a sensitive probe for hepatic Fc receptor function and has potential for human use.

Animals↗

[Activation of protein biosynthesis in rat organs and tissues during stimulation of the mononuclear phagocyte system with prodigiosan].

As shown earlier, the mononuclear phagocyte system (MPS) plays an important role in regulation of protein synthesis in different rat tissues. In vivo stimulation of MPS by lipopolysaccharide from Bacillus prodigiosum caused a significant increase of protein synthesis in the liver, lungs, adrenal glands, thymus, spleen and bone marrow. The results obtained suggest that MPS is involved in the regulation of tissue regenerative process at the level of physiological state.

Adrenal Glands↗

[Syndrome of activation of the mononuclear phagocyte system. Initial manifestation of visceral leishmaniasis].

We report a case of mononuclear phagocyte system activation observed in a 12 month-old girl presenting with fever, hepatosplenomegaly, pancytopenia, histiocytic hyperplasia with hemophagocytosis in the bone marrow, high triglyceride and low fibrinogen blood levels. This syndrome was associated with visceral leishmaniasis. We conclude that systemic leishmaniasis is a curable cause of disorders characterized by an activation of the mononuclear phagocyte system.

Animals↗

The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells.

There have been many attempts in the past to classify phagocytic mononuclear cells and to define the cell system they are considered to form-among these being the "macrophage system" of Metchnikoff, the "reticulo-endothelial system" of Aschoff, and the "reticulo-histiocyte system" proposed by Volterra and reintroduced by Thomas. None of these is entirely adequate in the light of present knowledge. In 1969, therefore, a group of workers proposed a new classification of all highly phagocytic mononuclear cells and their precursors in what they termed the "mononuclear phagocyte system". This system includes the promonocytes and their precursors in the bone marrow, the monocytes in the peripheral blood, and the macrophages in the tissues. Subsequent consultation with numerous other specialists throughout the world led to a certain number of changes in this classification, which is now proposed in revised form.Inclusion of cells in the "mononuclear phagocyte system" is based on similarities in the morphology, function, origin, and kinetics of the phagocytes. By these criteria reticular cells, dendritic cells, endothelial cells, and fibroblasts (fibrocytes) are excluded. The proponents point out that as new knowledge is acquired modifications may have to be made, certain cells being added to or removed from the new classification.

Bone Marrow Cells↗