RESUMEN
BACKGROUND: At the development of graft versus host disease in genetically homogeneous population of (C57BI/6 x DBA/2) Fl mice two clinical phenotypes of SLE-like disease were revealed: lupus+ (immune complex glomerulonephritis and hemnolytic anemia) and lupus - (hemolytic anemia). The GvHD phenotypic heterogeneity is determined by the Th2-polarization: Th2 lymphocyte predominant activity, leads to the lupus+development, or prevalence activity of Th1 cells, leads to the lupus- development. OBJECTIVE: Our aim was to evaluate the possibility of using an experimental model of autoimmnune disease for studying and testing of epigenetic modifications, shifting Th1/Th2 balance in vivo. METHODS: Chronic GVHD was induced in B6D2F1 mice by the transplantation of 130x10(6) parental DBA/2 splenocytes. Anti-ds-DNA, total IgG and IgGI, IgG2a Abs were measured by ELISA. RESULTS: Six- to 8-week-old female DBA/2 and B6D2F1 mice were obtained from Biological Research Laboratory (Novosibirsk). It was established that regular moderate physical activity (unladed swimming) shifted Th1/Th2 balance towards Th1. This leads to a decrease in a population of recipients the lupus+ mice from 57 to 26% (p <0,001) with significantly reduced hypergammaglobulinemia (IgG from 2,8 to 2,0 mg/ml; p <0,047) and DNA antibodies titer from 0,18 to 0,12 OD (p =0,05). Administration of epigenetic modificator bisphenol A at low doses, which mimicking estrogen effects, enhances the proportion of lupus+ mice in experimental groups from 33 to 64% (p <0,001) and impairs their clinical status by the increasing the urine protein level from 2.8 to 4,2 mg/ml (p <0,001) in animals. CONCLUSION: Th1/Th2 - balance presumably is determined by the immune system epigenetic modification in experimental mice, formed on the previous stages of ontogeny and defines the direction of immune processes development in individual animal.
Asunto(s)
Enfermedades Autoinmunes/genética , Autoinmunidad/genética , Epigenómica/métodos , Enfermedad Injerto contra Huésped/genética , Linfocitos T/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Enfermedad Injerto contra Huésped/inmunología , Inmunoglobulinas/inmunología , Túbulos Renales/inmunología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Bazo/inmunología , Bazo/trasplanteRESUMEN
AIM: Evaluate the effect of experimental hyperlipidemia on the intensity of development of acute graft-versus-host reaction (GVHR) in mice. MATERIALS AND METHODS: Half-allogenic system C57Bl/6 (C57Bl/6 x DBA/2)F1 was used as a laboratory model of acute GVHR. Experimental hyperlipidemia in mice-recipients was induced by repeated administration of poloxamer 407. RESULTS: Lethality in the group of mice with acute GVHR developing against the background of preceding hyperlipidemia was significantly higher (70% at day 50 of GVHR development) compared with control group with acute GVHR (50% lethality at day 50). Such effect on the degree of severity of acute GVHR induced under the conditions of hyperlipidemia is confirmed by a more pronounced destruction of thymus in mice of the group with previously induced hyperlipidemia. CONCLUSION: Preceding hyperlipidemia induced by administration of poloxamer 407 shifts Th1/2- balance in the development of acute GVHR towards Th1. Mechanisms of this effect and possible role of nuclear LXR receptors in regulation of immune reactions are discussed.
Asunto(s)
Reacción Injerto-Huésped/inmunología , Hiperlipidemias/inmunología , Balance Th1 - Th2 , Animales , Citotoxicidad Inmunológica , Humanos , Hiperlipidemias/inducido químicamente , Hiperlipidemias/patología , Ratones , Poloxámero/toxicidad , Bazo/inmunología , Bazo/patología , Timo/inmunología , Timo/patologíaRESUMEN
AIM: Approbation of laboratory model of hyperlipidemia induced by multiple administration of poloxamer 407 to hybrid mice (C57BL/6 x DBA/2) F1. MATERIALS AND METHODS: Two-month-old female mice (C57B1/6 x DBA/2)F1 were used for experiments. Level of dyslipidemia was assessed measuring cholesterol level in serum by method with cholesteroloxidase. RESULTS: Dosages and timing of administration of the compound for inducing stable moderate hypercholesterolemia were selected. It was discovered that dyslipidemia induced by this method accompanied by reliable increase of neutrophils count in peripheral blood of animals. CONCLUSION: Hyperlipidemia induced in mice by administration of poloxamer 407 could be used for convenient experimental model for complex studies of immune system functions during pathophysiologic conditions associated with lipid metabolism disorders.
Asunto(s)
Modelos Animales de Enfermedad , Hiperlipidemias/inducido químicamente , Hiperlipidemias/metabolismo , Ratones , Animales , Quimera , Femenino , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Poloxámero/farmacologíaRESUMEN
The influence of tumor necrosis factor a (TNF-alpha) and media, conditioned by activated macrophages and lymphocytes and containing a complex of biologically active compounds (including cytokines), on the parameters of lipid metabolism in macrophages was studied. The addition of recombinant TNF-alpha and immunocompetent cell-conditioned media to mouse peritoneal macrophages culture stimulated labelled oleate incorporation into cholesterol esters and triglycerides, as well as labelled glycerine incorporation into cholesterol esters, but inhibited labelled cholesterol incorporation into cholesterol esters. One of the mechanisms of the influence of activated immunocompetent cells on cholesterol metabolism in macrophages was, supposedly, the stimulation of sphigmomyelinase activity by a complex of anti-inflammatory cytokines produced by these cells on their activation.
Asunto(s)
Metabolismo de los Lípidos , Activación de Macrófagos , Macrófagos Peritoneales/inmunología , Animales , Animales no Consanguíneos , Células Cultivadas , Ésteres del Colesterol/química , Ésteres del Colesterol/metabolismo , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Citocinas/farmacología , Leucocitos/inmunología , Lípidos/química , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Bazo/inmunología , Triglicéridos/química , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Intravenous injection of acetylated low density lipoproteins (acLDL) in mice in a dose of 0.5 mg per mouse decreased the intensity of humoral immune response to sheep red blood cells (SRBC) by 35%. The addition of acLDL to mouse peritoneal macrophages in vitro resulted in inhibition of Fc-dependent phagocytosis of SRBC and fourfold increased secretion of prostaglandins E2 by macrophages. Fc-dependent phagocytosis of SRBC was also found to be inhibited by oxysterols (25-hydroxycholesterol and 7-ketocholesterol), added to the incubation medium of macrophages in vitro in doses of 0.5-5 mg/ml. The conclusion was made that oxidative metabolism of cholesterol and arachidonic acid, contained in LDL, may mediate the immunomodulating effects of modified LDL.
Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Lipoproteínas LDL/inmunología , Lipoproteínas LDL/farmacología , Activación de Macrófagos/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Activación de Macrófagos/efectos de los fármacos , Masculino , RatonesAsunto(s)
Hidroxicolesteroles/farmacología , Cetocolesteroles/farmacología , Linfocitos/efectos de los fármacos , Linfocinas/inmunología , Macrófagos/efectos de los fármacos , Adulto , Células Presentadoras de Antígenos/citología , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Adhesión Celular/inmunología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , División Celular/efectos de los fármacos , División Celular/inmunología , Células Cultivadas , Femenino , Antígenos HLA-DR/inmunología , Humanos , Activación de Linfocitos/inmunología , Prueba de Cultivo Mixto de Linfocitos , Linfocitos/citología , Linfocitos/inmunología , Macrófagos/citología , Macrófagos/inmunología , Masculino , Persona de Mediana EdadRESUMEN
The influence of benzo(a)anthracene (BA) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on functional properties of peripheral blood mononuclear cells (PBC) has been investigated. Incubation of mitogen-stimulated cells in the presence of xenobiotics induced high activity of benzo(a) pyrene-hydroxylase (BH) and suppressed lymphocyte blast transformation. Preincubation of unstimulated PBC with BA and TCDD caused insignificant increase of BH activity. The results show modulated effect of xenobiotics on functional properties of PBC.
Asunto(s)
Benzo(a)Antracenos/farmacología , División Celular/efectos de los fármacos , Dioxinas/farmacología , Activación de Linfocitos/efectos de los fármacos , Dibenzodioxinas Policloradas/farmacología , Linfocitos T/efectos de los fármacos , Benzopireno Hidroxilasa/análisis , Células Cultivadas , Humanos , Lectinas/farmacología , Formación de Roseta , Linfocitos T/citología , Linfocitos T/inmunologíaRESUMEN
Xenobiotics--inducers of benzo(a)pyrene hydroxylase (BPH)--exert different effects on mitogen-stimulated and mitogen-unstimulated human peripheral blood mononuclear cells (PBC). In mitogen-stimulated culture xenobiotics highly increase BPH activity and suppress cell blast transformation. The incubation of the unstimulated PBC in the presence of xenobiotics increases insignificantly BPH activity, intensifies T-cell differentiation and concanavalin A-induced proliferation. The BPH activity is mainly associated with the PBC adhered to plastic Petri dishes. However, the control and induced levels of BPH activity depend on the interaction between adhered and nonadhered cells.