RESUMO
Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.
Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Mitocôndrias , Humanos , Hepatite B Crônica/virologia , Hepatite B Crônica/patologia , Masculino , Feminino , Vírus da Hepatite B/patogenicidade , Adulto , Mitocôndrias/metabolismo , Pessoa de Meia-Idade , Contagem de Leucócitos , Leucócitos/metabolismo , DNA Viral/sangue , Potencial da Membrana Mitocondrial , Monócitos/metabolismo , Monócitos/imunologia , Monócitos/virologia , Monócitos/patologia , Neutrófilos/metabolismo , Neutrófilos/imunologiaRESUMO
Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.
Assuntos
Corynebacterium/fisiologia , Macrófagos/imunologia , Peptidoglicano/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Estimativa de Kaplan-Meier , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Peptidoglicano/farmacologia , Fagocitose , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Vancomicina/farmacologia , Vancomicina/uso terapêuticoRESUMO
AIM: To detect the rabbit-derived polyclonal antibodies against extracellular protein segments of human glucocorticoid-inducible tumor necrosis factor receptors (anti-hGITR(aa27-165);PcAb) with regard to its capacity of linkage to natural GITR molecules and the function on CD4(+); T cells. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated and cultured under stimulation; flow cytometry was applied to check the capacity of anti-hGITR(aa27-165);PcAb for linkage to natural GITR molecules on PBMCs; human CD4(+); T cells were isolated by immunological magnetic beads and (3);H-TdR incorporation tests were performed to observe improving-proliferation action of anti-hGITR(aa27-165);PcAb while CD4(+); T cells were cultured with or not with some cytokines. RESULTS: Anti-hGITR(aa27-165);PcAb was able to bind GITR molecules with natural conformation in a concentration-dependent way; furthermore, this PcAb could improve the reproduction of CD4(+); T cells. CONCLUSION: The rabbit-derived anti-hGITR(aa27-165);PcAb prepared in our laboratory is capable of linking to natural target molecules and possesses the activation function upon CD4(+); T cells, the further exploration should allow for its applications for diagnosis and treatment of relavent diseases.