RESUMO
Dendritic cells isolated from thymus and tonsil were tested for susceptibility to HIV-1 strains that are tropic for macrophages or for T cell lines. DCs were purified by cell sorting and before infection expressed high levels of CD4 and HLA-DR and lacked markers for T, B, NK cells, or macrophages. Viral entry and reverse transcription was found after pulsing with strains of HIV-1 that could infect macrophages. During the first 36 h the PCR signals for gag sequences increased in DCs and macrophages. In contrast little if any viral DNA was found after pulsing macrophages or DCs with HIV-1 that was able to infect T cell lines. DCs pulsed with HIV-1 were able to transmit infection to responding T cells during an allogeneic or superantigen response. Selection for virus able to infect lymphoid DCs and other DCs expressing CD4 and its transfer to T cells during subsequent immune responses may provide a mechanism for the observed predominance of macrophage-tropic HIV-1 after in vivo transmission.
Assuntos
Células Dendríticas/virologia , HIV-1/crescimento & desenvolvimento , Tonsila Palatina/virologia , Timo/virologia , Antígenos CD4/análise , Separação Celular , Criança , Genes gag , Transcriptase Reversa do HIV , Antígenos HLA-DR/análise , Humanos , Macrófagos/virologia , Tonsila Palatina/citologia , DNA Polimerase Dirigida por RNA/metabolismo , Linfócitos T/virologia , Timo/citologia , Transcrição GênicaAssuntos
Células Dendríticas/imunologia , Células Dendríticas/virologia , HIV-1/imunologia , Síndrome da Imunodeficiência Adquirida/etiologia , Animais , Antígenos CD4/metabolismo , Efeito Citopatogênico Viral , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/patogenicidade , Humanos , Técnicas In Vitro , Macrófagos/imunologia , Macrófagos/virologia , Camundongos , Linfócitos T/imunologia , Linfócitos T/virologia , Timo/imunologia , Timo/virologiaRESUMO
Polymorphonuclear neutrophil (PMN) accumulation within damaged tissues, a hallmark of acute inflammation, is dependent upon initial adhesion to endothelial cells. In vitro studies suggest that P-selectin and platelet activating factor (PAF) are key molecules in this process by promoting the initial adhesion of PMN to endothelial cells. We report in vivo studies in which intravenous administration of lipopolysaccharide (LPS) to anesthetized rats caused a very rapid onset (< 5 min) of neutropenia, in association with induction of surface expression of P-selectin on microvascular endothelial cells in kidney, liver and lung; analogous induction of P-selectin expression by cultured endothelial cells was observed in response to LPS stimulation in vitro. In addition, treatment with an antibody (Ab) to P-selectin (or use of a PAF antagonist) blocked development of neutropenia in vivo for at least 15 min post-LPS injection, and Ab treatment was shown to block PMN accumulation in tissues. These studies document roles for P-selectin and PAF in the early adhesion of PMN to endothelial cells in vivo.