Effect of hyperlipidemia on functional activity of peritoneal macrophages in CBA and C57Bl/6 mice

The effect of experimental hyperlipidemia on functional activity of macrophages was studied in CBA and C57Bl/6 mice resistant and sensitive to the formation of aorta lesions, respectively. Two-month atherogenic diet increased the content of cholesterol in the serum and cells of peritoneal exudate in mice of both strains. In parallel, production of nitrites and 5'-nucleotidase activity in peritoneal macrophages increased, while parameters of phagocytosis, pinocytosis, and NBT test remained unchanged. Changes in the state of macrophages can be explained by increased cholesterol content. The absence of differences in functional activity of macrophages in CBA and C57Bl/6 mice indicates that the observed shifts are insignificant for the development of fatty streaks in the aorta.     

Effect of Hyperlipoproteinemia on Functional Activity of Peritoneal Macrophages during Tumor Growth

The role of hypercholesterolemia as a factor modulating functional activity of macrophages during the growth of syngeneic transplanted 22a hepatoma in mice was studied. Starting from day 21 after inoculation of tumor cells we observed the development of hyperlipoproteinemia paralleled by an increase in macrophage activity parameters. The total serum cholesterol content and production of nitroxide anions by macrophages were in positive correlation on days 14-35 of tumor growth. We hypothesized that the development of hypercholesterolemia at the late stages of some tumor growth is a factor stimulating production of nitrites and 5'-nucleotidase activity.     

Effect of metabolic factors on apoptosis in thymocytes during tumor growth

Intensive apoptotic death of thymocytes is a possible mechanism of thymus involution during tumor growth. We studied the role of hypercholesterolemia and lactate acidosis in the induction of increased sensitivity of thymocytes to apoptosis during growth of transplanted hepatoma 22a in mice. Spontaneous apoptosis in thymocytes during tumor growth in mice was studied in vitro by acridine orange/ethidium bromide staining and diphenylamine test. Plasma levels of lactate, total cholesterol, -cholesterol, and triglycerides were measured. A positive correlation was found between intensification of apoptosis (diphenylamine test) and increased concentration of total plasma cholesterol on days 21 and 28 after inoculation of tumor cells. Plasma lactate content did not increase at this term. We hypothesize that hypercholesterolemia accompanying tumor growth acts as a factor increasing thymocyte sensitivity to apoptosis.     

Assessment of activity of tumor necrosis factor under normal conditions and in ovarian tumors

Department of Immunology, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR R. V. Petrov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 6, pp. 571–573, June, 1990.     

Isoenzyme profile of lactate dehydrogenase in the cranial cervical sympathetic ganglion under normal conditions and during synaptic blockade

The isoenzyme profile of lactate dehydrogenase in the cranial cervical sympathetic ganglion of rabbits was studied under normal conditions and during blockade of nicotinic cholinergic synapses. Under normal conditions this profile was presented by 5 isoforms of the enzyme (lactate dehydrogenases 1, 2, 3, 4, and 5). Activity of H-isoforms prevailed. Blockade was accompanied by heterotropic allosteric inhibition of lactate dehydrogenase isoforms. H-and M-isoforms underwent simultaneous changes. Activity of H-isoforms sharply decreased. However, the ratio between lactate dehydrogenases 1 and 2 during complete or partial blockade did not differ from that observed in experiments with the intact ganglion. M-isoforms (lactate dehydrogenases 4 and 5) disappeared during partial blockade. Activity of hybrid lactate dehydrogenase 3 significantly decreased and was undetected during partial and complete blockade, respectively. Our results indicate that enzyme activity and isoenzyme profile of lactate dehydrogenase are determined by function of nicotinic synapses. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 140, No. 12, pp. 642–644, December, 2005     

Effect of tuftsin on the functional activity and intracellular pH of murine peritoneal macrophages

The effect of tuftsin and its tripeptide analog in various concentrations (from 0.001 to 10.0 μg/ml) on phagocytosis and on the intracellular pH is studied in murine peritoneal macrophages. Tuftsin causes a uniform dose-dependent increase of these two parameters in the cells. This effect is maximally pronounced at concentrations of the peptide close to its physiological level (about 0.3 μg/ml) and gradually decreases as its content in the incubation medium is lowered or raised. On the other hand, the tripeptide analog of tuftsin does not exhibit such an effect on the cells and under the same conditions suppresses phagocytosis and acidifies their intracellular medium. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 265–267, March 1994 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Phenotypic characterization and functional activity of human milk macrophages

A large population (about 80%) of the cells obtained from colostrum and early human milk were considered to be macrophages by the following criteria: nonspecific esterase stain, adherence, phagocytosis and IgG-Fc receptor expression. The majority of freshly isolated human milk macrophages (HMM phi) stain for the monocyte antigen OKM1. Another monocyte antigen, 61D3, was expressed only by 30% of HMM phi. Class II antigens were expressed by HMM phi. About 85% of the cells were DR-positive whereas 50% were DS-positive as assessed with a panel of monoclonal antibodies directed against class II antigens. Monocyte and class II antigens were gradually lost during in vitro culture. HMM phi can support proliferative response to antigens and mitogens when cocultured with autologous peripheral T cells. The proliferative response was significantly reduced when monoclonal antibodies to DR or DS were added to the assay. These results indicate that HMM phi have the phenotype and functional characteristics of antigen presenting cells.     

Cell surface receptors for lactate dehydrogenase-elevating virus on subpopulation of macrophages

We examined the binding and internalization of unlabeled and 125I-labeled, purified lactate dehydrogenase-elevating virus (LDV) by peritoneal macrophages cultured in vitro. Upon incubation of the cells at 4 degrees C with greater than 100 ID50/cell, the virus was surface-bound on a small subpopulation of macrophages (about 5% of the total cells) as determined by electron microscopy, fluorescent antibody staining, and autoradiography of cells incubated with 125I-labeled LDV. At 37 degrees C, LDV particles were seen in intracellular endocytic vesicles also in about 5% of the cells, and the proportion of cells with virus-containing vesicles correlated with the proportion of cells which became productively infected with LDV as assessed by determining LDV RNA synthesis in individual cells and by fluorescent antibody staining. Pretreatment of the resident peritoneal macrophages with trypsin inhibited the binding of 125I-labeled LDV and the productive infection of the cells with the virus. After removal of the trypsin and incubation in complete medium, permissiveness for LDV reappeared after an 8-12 h lag, whereas Fc and C3 receptors reappeared more rapidly after trypsin treatment. Populations of resident peritoneal macrophages, starch-elicited peritoneal macrophages, splenic macrophages, and bone marrow macrophages contained a similar proportion of cells that could be productively infected with LDV. Little, if any, LDV replication was detected in cultures of lung, liver and peripheral blood macrophages as well as in thioglycollate-elicited and BCG-activated macrophages. We conclude that the permissiveness for LDV of resident peritoneal macrophages correlates with the presence of a trypsin-sensitive receptor present on a subpopulation of these cells. The identity of the receptor has not been definitively established. Treatment of macrophages with neuraminidase or various sugars had no significant effect on LDV replication. Lysis of I-A-positive macrophages with a monoclonal antibody and complement reduced the number of macrophages which could be productively infected by 50%, which suggests that macrophages lacking surface Ia can be productively infected with LDV in vitro.     

Effect of vitamin D on humoral and cell-mediated immune response and functional activity of peritoneal macrophages

1,25-Dihydroxyvitamin D₃, an active metabolite of vitamin D, decreases the number of antibody-producing cells in C57B1/6 mice immunized with sheep erythrocytes, suppresses lymphocytes proliferation in response to stimulation with pokeweed mitogen and concanavalin A, and stimulates functional activity of macrophages. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 63–65, January, 1997     

Effect of mineral dust on generation of superoxide radicals and hydrogen peroxide by alveolar macrophages,granulocytes, and monocytes

Clinical Laboratory, Research Institute of Work Hygiene and Occupational Diseases, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. F. Izmerov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 10, pp. 372–375, October, 1990.     

Longitudinal study of tumor-associated macrophages during tumor expansion using MRI

MRI is being used increasingly for the noninvasive longitudinal monitoring of cellular processes in various pathophysiological conditions. Macrophages are the main stromal cells in neoplasms and have been suggested to be the major cell type ingesting superparamagnetic iron oxide (SPIO) nanoparticles. However, no MRI study has described longitudinally the presence of tumor-associated macrophages (TAMs) during tumorigenesis with histological confirmation. To address this, we injected SPIO nanoparticles into the circulation of tumor-bearing mice and used MRI and post-mortem histology to monitor TAMs at different time points. The MRI results demonstrated that TAMs, as hypointense signals, appeared continually with the expansion of the tumor. The histological findings also revealed that SPIO-labeled TAMs tended to deposit closer to the vessel lumen with time prior to rapid tumor growth. The present study demonstrates the potential of using MRI to assess longitudinally TAM accumulation during tumorigenesis, and provides the first in vivo insight into the topographical arrangement of TAMs in relation to the progression of tumors. In vivo monitoring of the presence of TAMs could be useful for the development of tumor treatments that target TAM functions.     

Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress

Tumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKα. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors.     

Reactivity of alveolar macrophages during granulomatous inflammation of the lungs under conditions of acute massive blood loss

Reactivity of mouse alveolar macrophages by their ability to phagocytize killed St. aureus bacteria and production of reactive oxygen metabolites (nitro blue tetrazolium test) in response to zymosan administration was studied under normal conditions and after acute massive blood loss. Zymosan-induced granulomatous inflammation of the lungs during acute massive blood loss 2-fold inhibited the increase in oxidative metabolism of alveolar macrophages. Suppressed production of toxic oxygen radicals in alveolar macrophages was accompanied by accelerated recovery of cells on the surface of the respiratory tract.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 257–260, September, 2004     

Reactivity of alveolar macrophages during granulomatous inflammation of the lungs under conditions of acute massive blood loss

Reactivity of mouse alveolar macrophages by their ability to phagocytize killedSt. aureus bacteria and production of reactive oxygen metabolites (nitro blue tetrazolium test) in response to zymosan administration was studied under normal conditions and after acute massive blood loss. Zymosan-induced granulomatous inflammation of the lungs during acute massive blood loss 2-fold inhibited the increase in oxidative metabolism of alveolar macrophages. Suppressed production of toxic oxygen radicals in alveolar macrophages was accompanied by accelerated recovery of cells on the surface of the respiratory tract. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 257–260, September, 2004     

Effect of pravastatin, simvastatin and atorvastatin on the phagocytic activity of mouse peritoneal macrophages

Since cholesterol and lipid content may affect cell membrane fluidity, we assumed that treatment of mice with lipid lowering statins would enhance the engulfing capacity of their macrophages. Four groups of animals were examined. Group I-treated with pravastatin, group II--with simvastatin--both drugs in a dosage of 40 mg/kg daily, 5 days/week for a total of 3 weeks. Mice in group III received atorvastatin 5 mg/kg for the same time period. Group IV--untreated animals serving as controls. The phagocytic capacity of the peritoneal macrophages was evaluated by their ability to engulf latex particles. In addition, the mitogen response of the peripheral blood mononuclear cells (PBMC) and splenocytes to Con A and PHA was examined. Compared to the controls, the percentage of phagocyting cells in pravastatin-treated mice was enhanced by 18%, with simvastatin--by 24% and in atorvastatin-treated animals by 8%. The three statins increased the phagocytic index by 79.5%, 88.8% and 62%, respectively. The mitogen response of splenocytes from mice treated with the three statins to Con A increased by 68%, 48% and by 40%, respectively. Compared with the controls the response to PHA was higher in animals treated with pravastatin (84%), simvastatin (73%) and atorvastatin (57%). The response of PBMC from statin-treated animals to both mitogens did not differ from that of the controls. The results suggest that statins, at least those hereby investigated, may exert a beneficial effect on the immune function of the macrophages.