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.     

Function of the mononuclear phagocyte system after administration of emulsions of perfluorinated carbon compounds

Morpho-functional characteristics of mononuclear phagocyte system (MPS) have been studied in experimental animals upon the infusions of perfluorocarbon (PFC) emulsions. It has been established that the infusion of high doses of PFC emulsions following massive hemorrhage causes the reduction in the histoenzymatic activity in MPS of PFC-accumulating organs. Low doses of PFC emulsions increase histochemical activity in PFC-containing macrophages, suggesting a stimulating effect of PFC emulsions on MPS.     

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).     

The CNS mononuclear phagocyte system in health and disease

1. Download : Download high-res image (94KB)
2. Download : Download full-size image

     

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.     

Effect of estrone on formation of the focus of heterotopic hematopoiesis

The effect of estrone injections on the heterotopic bone marrow organ formation was studied in (C57Bl X CBA)F1 mice by bone marrow shaft transplantation under the kidney capsule. Estrone injections resulted in femur marrow fibrosis, the increase in the weight of femur and heterotopic organ ossicle, drastic reduction in heterotopic organ cellularity. Depression of hemopoiesis in ectopic organ cannot be attributed to mechanical displacement of hemopoietic cells because a newly formed bone cavity under the kidney capsule was not closed. Thus, estrone had a detrimental effect on the creation of microenvironment in the heterotopic organ.     

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 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.     

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.     

Effects on the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid A compared with empty liposomes

In experiments designed to examine the adverse effects of chronic liposome administration in vivo on the mononuclear phagocyte system (reticuloendothelial system), the presence of drug entrapped in the liposomes may increase the level of reticuloendothelial impairment. We have compared the effects on the mononuclear phagocyte system in mice of chronic administration of empty liposomes with the effects of liposomes containing the anti-leishmanial drug meglumine antimoniate. We have also examined the effect on the mononuclear phagocyte system of continued injections of liposomes containing lipid A, a component of bacterial lipopolysaccharide, which is responsible for macrophage activation. Ten intravenous injections of multilamellar liposomes composed of dipalmitoylphosphatidylcholine and cholesterol (1:0.75 M ratio) were given to ICR mice over a 25-day period. Two individual groups of mice received endotoxin-free liposomes in which meglumine antimoniate was either present or absent. One addition group received liposomes containing lipid A derived from Escherichia coli lipopolysaccharide. A control group received sterile saline injections. In each group, a depression of the phagocytic index, as measured by reduction of uptake of particulate carbon, was observed among some of the individual animals 24 h after the first injection. In many mice a marked splenomegaly was observed. A depressed phagocytic index and splenomegaly were most marked for mice receiving lipid A liposomes. However, there was a large individual variability among mice receiving these preparations and some mice in each group had normal spleen size and a nearly normal phagocytic index. Tissue distribution of liposomes containing [14C]dipalmitoylphosphatidylcholine as a phospholipid marker was examined in all groups in mice 24 h after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.