RESUMO
Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow. In this study, DCs (CD11c(+) cells) differentiated from the bone marrow of mice with inflammation of the airways, or the peritoneal cavity had poor priming ability resulting in reduced, long-lived responses to that antigen in vivo. This indicates enhancement of regulatory mechanisms of immune responses through a peripheral tissue-bone marrow axis. If CD11c(+) cells, expanded from the bone marrow of mice with tissue inflammation were antigen pre-loaded and injected into mice already sensitized to that antigen, then subsequent contact hypersensitivity responses were significantly reduced. The effects of inflammation were imprinted in vivo and were independent of in vitro culture conditions for DC differentiation. The effect of tissue inflammation on the bone marrow DC precursors was not detected in mice treated subcutaneously with slow-release indomethacin pellets, suggesting a role for prostanoids, including prostaglandin E(2), in differentiation of regulatory CD11c(+) cells from bone marrow. Our study represents an important homeostatic process with potential for therapeutic use in the future.
Assuntos
Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Células Dendríticas/imunologia , Homeostase/imunologia , Inflamação/patologia , Pulmão/patologia , Cavidade Peritoneal/patologia , Compostos de Alúmen , Animais , Antígeno B7-2/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Antígeno CD11c/metabolismo , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/imunologia , Apresentação Cruzada/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/enzimologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Haptenos/imunologia , Homeostase/efeitos dos fármacos , Hipersensibilidade/complicações , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Imunização , Indometacina/farmacologia , Inflamação/complicações , Inflamação/imunologia , Interleucina-4/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pneumopatias/complicações , Pneumopatias/imunologia , Pneumopatias/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Proteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mielopoese/efeitos dos fármacos , Ovalbumina/imunologiaRESUMO
This study was designed to determine the sensitivity and reproducibility of recovering anti-streptolysin O titres (ASOT) from dried blood spot (DBS) samples, a methodologic subcomponent of the penicillin pharmacokinetic studies in children receiving secondary prophylaxis with intramuscular benzathine penicillin for acute rheumatic fever.