Asunto(s)
Adipocitos/metabolismo , Apolipoproteínas E/metabolismo , Hierro/metabolismo , Adipocitos/efectos de los fármacos , Apolipoproteínas E/antagonistas & inhibidores , Arritmias Cardíacas/metabolismo , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Compuestos Férricos/farmacología , Factor 1 de Crecimiento de Fibroblastos/farmacología , Enfermedades Genéticas Ligadas al Cromosoma X/metabolismo , Gigantismo/metabolismo , Cardiopatías Congénitas/metabolismo , Humanos , Discapacidad Intelectual/metabolismo , Estrés Oxidativo/efectos de los fármacos , Cultivo Primario de Células , Proteómica , Compuestos de Amonio Cuaternario/farmacologíaRESUMEN
INTRODUCTION: Endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However the mechanism by which injury develops remains unclear. We hypothesized that hepatic macrophages are pivotal in the development of endotoxin-induced biliary injury and that no injury would occur in their absence. MATERIAL AND METHODS: Clodronate liposomes were used to deplete macrophages from the liver. Forty-eight rats were equally divided across six study groups: sham operation (sham), liposome treatment and sham operation (liposomes+sham), 1mg/kg LPS i.p. (LPS), liposome treatment and LPS administration (liposomes+LPS), hepatic ischaemia-reperfusion injury with LPS administration (IRI+LPS) and liposome treatment followed by IRI+LPS (liposomes+IRI+LPS). Following 6h of reperfusion, blood, bile, and liver tissue was collected for further analysis. Small bile duct injury was assessed, serum liver tests were performed and bile composition was evaluated. The permeability of the blood-biliary barrier (BBB) was assessed using intravenously administered horseradish peroxidase (HRP). RESULTS: The presence of hepatic macrophages was reduced by 90% in LPS and IRI+LPS groups pre-treated with clodronate liposomes (P<0.001). Severe small bile duct injury was not affected by macrophage depletion, and persisted in the liposomes+IRI+LPS group (50% of animals) and liposomes+LPS group (75% of animals). Likewise, BBB impairment persisted following macrophage depletion. LPS-induced elevation of the chemokine Mcp-1 in bile was not affected by macrophage depletion. CONCLUSIONS: Depletion of hepatic macrophages did not prevent development of biliary injury following LPS or LPS-enhanced IRI. Cholangiocyte activation rather than macrophage activation may underlie this injury. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Asunto(s)
Enfermedades de los Conductos Biliares/inmunología , Conductos Biliares/patología , Células Epiteliales/inmunología , Macrófagos/inmunología , Daño por Reperfusión/inmunología , Animales , Bilis/efectos de los fármacos , Bilis/metabolismo , Conductos Biliares/citología , Conductos Biliares/inmunología , Quimiocina CCL2/inmunología , Quimiocina CCL2/metabolismo , Ácido Clodrónico/farmacología , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Humanos , Lipopolisacáridos/toxicidad , Liposomas , Hígado/irrigación sanguínea , Hígado/citología , Macrófagos/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicacionesRESUMEN
Growing numbers of technology assisted children are indefinitely hospitalized due to factors related to lack of parental and societal support. By describing the needs of one child, recommendations for providing comprehensive chronic inpatient care and strategies for securing long-term placement for the indefinitely hospitalized child are presented.
