Endocytosis by liver cells during stimulation of the mononuclear phagocyte system by yeast polysaccharides]

Endocytosis (phagocytosis, fluid-phase- and receptor-mediated endocytosis) by liver cells, lysosomal enzyme activities have been studied during macrophages stimulation by yeast polysaccharides. It was shown that like macrophages stimulator zymosan, yeast polysaccharides cryelan and rhodexman increased the carbon particles phagocytosis. The most effective was intravenous administration of yeast polysaccharides. Compared to rhodexman, the effect of cryelan was more prominent. Macrophages stimulation was followed by suppression of fluid-phase endocytosis by liver cells. Increased activity of cathepsin B was discovered on day 5 after macrophages stimulation (proteinase, most typical for macrophages enzymes).     

Functional restructurings of the mononuclear phagocyte system in experimental liver cirrhosis

In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50-fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis.     

The tissue heterogeneity of mononuclear phagocyte system cells interacting with Yersinia pestis

The work deals with the determination of the heterogeneity of cells of the mononuclear phagocyte system, localized in different tissues, in their interaction with Y. pestis. The macrophage populations under study have been found to be heterogeneous in their phagocytic activity with respect to Y. pestis. The digestive activity of alveolar macrophages is considerably lower than that of macrophages localized in other tissues. Macrophages obtained from different tissue are heterogeneous also in the intensity of changes in oxygen-dependent metabolic processes during their contacts with Y. pestis. Alveolar macrophages are less active in this respect than peritoneal ones. Alveolar macrophages under study have been shown to have their own characteristic features; for this reason, the data obtained in the study of one of these populations should not be extrapolated to other populations.     

Differential immunohistochemical resolution of the human mononuclear phagocyte system

Four new monoclonal antibodies, termed Ki-M1, Ki-M2, Ki-M3, and Ki-M4, were developed for distinguishing macrophage subgroups. Purified lysosomes of cells of stimulated U-937 cell line were used as immunogen. Specificity control was performed by staining unfixed cryostat sections of fresh human tissue with an immunohistochemical method, which allowed reliable recognition of reactive structures. Ki-M1 reacted with macrophages of lymphoid tissue, lung, and serous cavities. Ki-M2 recognized Kupffer cells and splenic macrophages. Both monoclonal antibodies reacted with interdigitating reticulum cells and Langerhans cells, which are thought to be accessory cells of the T-cell immune response. Accessory cells of the B-cell immune response, on the other hand, showed reactivity with Ki-M3 and Ki-M4. Thus, analogous to T lymphocytes, the human mononuclear phagocyte system (MPS) can be subdivided into different subgroups with the aid of appropriate monoclonal antibodies.     

Accessory cell function of cells of the mononuclear phagocyte system isolated from mycobacterial granulomas

Epithelioid cells from BCG-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas were examined for their ability to act as accessory cells for T-cell proliferation to mitogen (Con A) and antigen (PPD). The granuloma cells were separated on a FACS using monoclonal antibody specific to guinea pig macrophages. Epithelioid cells (which are Ia negative) were able to support proliferation to Con A but not to antigen. Cultures containing Ia positive granuloma macrophages from M. leprae sensitized animals did not show responsiveness to Con A or to PPD. Oil-induced peritoneal exudate macrophages from BCG or M. leprae immunized animals were able to act as accessory cells for both mitogen and antigen proliferation. The nonresponsiveness of cultures containing epithelioid cells stimulated with PPD or M. leprae granuloma macrophages stimulated with Con A was not due to suboptimal or supraoptimal accessory cell:lymphocyte ratios.     

The CNS mononuclear phagocyte system in health and disease

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The response of the mononuclear phagocyte system to chronic hyperglycemia

In this study we revealed a common reaction of cells of the mononuclear phagocyte system in the central and peripheral immunopoietic organs and pancreas in rats with chronic hyperglycemia. The activation of monocytopoiesis and recruitment of mononuclear phagocytes in peripheral tissues were observed. The modulation of the functional activity of mononuclear phagocytes by 3-aminophthal-hydrazide contributed to the normalization of monocytopoietic intensity and a decrease in the level of macrophagal infiltration in the thymus, pancreas, and peripancreatic lymph nodes. These changes indicate that mononuclear phagocytes are involved in the adaptive response to chronic hyperglycemia.     

Interleukin 1 and prostaglandin production by cells of the mononuclear phagocyte system isolated from mycobacterial granulomas

A study has been made of the activity of interleukin 1 (IL-1) and prostaglandins (PGs) in the culture supernatants from unstimulated and lipopolysaccharide (LPS)-stimulated mycobacteria-induced granuloma cells. Both epithelioid cells from bacillus Calmette-Guerin (BCG)-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas, separated on a fluorescence-activated cell sorter using monoclonal antibody specific to guinea pig macrophages, spontaneously secreted low levels of IL-1 (assayed by thymocyte comitogenic and fibroblast mitogenic activities) into culture supernatants. However, culture supernatants from LPS-stimulated epithelioid cells showed significantly higher IL-1 activity than those from unstimulated cells. In contrast, LPS stimulation of M. leprae granuloma macrophages failed to enhance IL-1 production. Nevertheless, IL-1 activity in the culture supernatants from stimulated mycobacterial granuloma cells of both types was much lower than that from LPS-stimulated peritoneal exudate macrophage culture supernatants. There was no detectable amount of prostaglandin E2 (PGE2) in the culture supernatants from both unstimulated and LPS-stimulated BCG- and M. leprae-induced granuloma cells in comparison to much higher levels of PGE2 produced by unstimulated (0.28-6.2 ng/ml) or LPS-stimulated (greater than 15 ng/ml) peritoneal exudate macrophages. However, BCG granuloma cells either secreted prostaglandin F2 alpha (PGF2 alpha) spontaneously or produced comparable levels of PGF2 alpha to those from peritoneal exudate macrophages on stimulation, while M. leprae granuloma macrophages produced much lower levels of PGF2 alpha.     

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.     

Use of liposomes to demonstrate the function of the mononuclear phagocyte system

The possibility of using liposomes containing an indicator composition (dye or fluorophor) for the determination of the eliminative activity of the system of mononuclear phagocytes (SMP) was studied. Liposomes were obtained by the sonication of the suspension of lecithin, cholesterol and an indicator substance. The rate of the elimination of liposomes from the blood stream after their intravenous injection into Wistar rats (males) was evaluated photometrically or fluorometrically in hemolyzed blood samples taken from the animals at different periods after the injection. The data thus obtained were processed by means of a microcomputer with the use of a specially developed program. The results of this investigation suggest that liposomes can be used for the study of the eliminative activity of SMP.     

Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation

The expression of transferrin receptors by blood monocytes, human alveolar macrophages, and in vitro matured macrophages was evaluated by immunofluorescence, radioligand binding, and Northern analysis, using the monoclonal anti-human transferrin receptor antibody OKT9, [125I]-labeled human transferrin and a [32P]-labeled human transferrin receptor cDNA probe, respectively. By immunofluorescence, the majority of alveolar macrophages expressed transferrin receptors (86 +/- 3%). The radioligand binding assay demonstrated the affinity constant (Ka) of the alveolar macrophage transferrin receptor was 4.4 +/- 0.7 X 10(8) M-1, and the number of receptors per cell was 4.4 +/- 1.2 X 10(4). In marked contrast, transferrin receptors were not present on the surface or in the cytoplasm of blood monocytes, the precursors of the alveolar macrophages. However, when monocytes were cultured in vitro and allowed to mature, greater than 80% expressed transferrin receptors by day 6, and the receptors could be detected by day 3. Consistent with these observations, a transferrin receptor mRNA with a molecular size of 4.9 kb was demonstrated in alveolar macrophages and in vitro matured macrophages but not in blood monocytes. Thus, although blood monocytes do not express the transferrin receptor gene, it is expressed by mature macrophages, an event that probably occurs relatively early in the process of monocyte differentiation to macrophages.