RESUMO
The aim of study was to investigate the effect of hypoxia on the macrophage phenotype and phenotypic plasticity and to determine the resistance to acute hypoxia in C57/BL mice, which have the pro-inflammatory M1 macrophage phenotype, and in BALB/c mice, which have the anti-inflammatory M2 macrophage phenotype. The following results were obtained. 1) The response of macrophages to acute hypoxia has two successive phases, the immediate, anti-inflammatory phase, and the delayed, pro-inflammatory phase. This response was more distinctly inverted in C57/BL6 M1 macrophages than in BALB/c M2 macrophages; 2) the effect of acute hypoxia on macrophage phenotypic plasticity depends on the genetically predetermined, original macrophage phenotype. In this process, a clear regularity was observed: hypoxia increased the capability of macrophages for changing into the pro-inflammatory M1 phenotype, while their capability for changing into the anti-inflammatory M2 phenotype remained virtually unaffected. 3) BALB/c mice were more resistant to acute hypoxia than C57/BL6 mice. Taken together, these data expand our understanding of mechanisms for pathogenetic effects of hypoxia.
Assuntos
Resistência à Doença/genética , Hipóxia/imunologia , Macrófagos/patologia , Doença Aguda , Imunidade Adaptativa/genética , Animais , Forma Celular/genética , Resistência à Doença/imunologia , Hipóxia/genética , Hipóxia/patologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fenótipo , Especificidade da EspécieRESUMO
Experiments on immortalized hippocampal cell culture of mice showed that afobazole increases the NGF level in a final concentration of 10(-8) M and the BDNF level in final concentrations from 10(-8) to 10(-5) M.
Assuntos
Ansiolíticos/farmacologia , Benzimidazóis/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Morfolinas/farmacologia , Fator de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Animais , Linhagem Celular , Hipocampo/citologia , Camundongos , Neurônios/metabolismoRESUMO
A lesser resistance against myocardial infarction (MI) in the Wistar rats as compared with the August rats was found to be combined with a greater stress-response and activation of the heart sympathetic regulation in the former rats. In the Wistar rats and not in August rats, an activation of hypothalamic noradrenaline (NA) system occurs as well as a greater "output" of the NA from sympathetic terminals in the myocardium. Accumulation of the HSP 70 stress-proteins in IM in the myocardium is nearly 2-2.5-fold lesser in the Wistar rats. Thereupon, different resistance against the IM in Wistar and August rats seems to be due to a genetically determine differences in intensity of the stress-response, activation of the heart sympathetic regulation in the IM, and production of the HSP 70 protective stress-proteins in the myocardium.