RESUMO
Whether or not NO plays a critical role in murine CMV (MCMV) infection has yet to be elucidated. In this study, we examined the role of NO in acute infection with MCMV using NO synthase type 2 (NOS2)-deficient mice. NOS2(-/-) mice were more susceptible to lethal infection with MCMV than NOS2(+/+) mice and generated a much higher peak virus titer in the salivary gland after acute infection. A moderate increase in the MCMV titer was also observed in other organs of NOS2(-/-) mice such as the spleen, lung, and liver. The immune responses to MCMV infection including NK cell cytotoxicity and CTL response in NOS2(-/-) mice were comparable with those of NOS2(+/+) mice. Moreover, the ability to produce IFN-gamma is not impaired in NOS2(-/-) mice after MCMV infection. The peritoneal macrophages from NOS2(-/-) mice, however, exhibited a lower antiviral activity than those from NOS2(+/+) mice, resulting in an enhanced viral replication in macrophages themselves. Treatment of these cells from NOS2(+/+) mice with a selective NOS2 inhibitor decreased the antiviral activity to a level below that obtained with NOS2(-/-) mice. In addition, the absence of NOS2 and NOS2-mediated antiviral activity of macrophages resulted in not only an enhanced MCMV replication and a high mortality but also a consequent risk of the latency. It was thus concluded that the NOS2-mediated antiviral activity of macrophages via NO plays a protective role against MCMV infection at an early and late stage of the infection.
Assuntos
Infecções por Herpesviridae/enzimologia , Infecções por Herpesviridae/imunologia , Muromegalovirus/imunologia , Óxido Nítrico Sintase/fisiologia , Doença Aguda , Animais , Citotoxicidade Imunológica/genética , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/mortalidade , Interferon gama/biossíntese , Células Matadoras Naturais/enzimologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muromegalovirus/crescimento & desenvolvimento , Óxido Nítrico Sintase/deficiência , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Taxa de Sobrevida , Linfócitos T Citotóxicos/enzimologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/virologia , Carga Viral , Ensaio de Placa Viral , Latência Viral/imunologia , Replicação Viral/imunologiaRESUMO
Botulinum neurotoxin type A (BoNT/A, 1.5 nM) completely inhibited indirectly evoked twitches in in vitro mouse phrenic nerve-diaphragm preparations within 40 - 45 min. Black tea extract, thearubigin fraction (TRB), mixed with BoNT/A blocked the inhibitory effect of the toxin. The protective effect of TRB extended to botulinum neurotoxins types B and E (BoNT/B and BoNT/E) and tetanus toxin, but not to tetrodotoxin. TRB was also effective against oral toxicity of BoNT/A, B and E. Thus, TRB may be of potential benefit in protecting the paralytic actions of botulinum neurotoxins (BoNTs), but its use is limited by mixing with the toxin.
