RESUMEN
Cholangiocytes function as antigen-presenting cells with CD1d-dependent activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro- and anti-inflammatory in liver immunopathology. We explored this immune pathway and the antigen-presenting potential of NKT cells in the bile ducts by challenging wild-type and Cd1d-/- mice with intrabiliary injection of the NKT cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated activation was performed with a monoclonal antibody. Intrabiliary oxazolone injection in wild-type mice caused acute cholangitis with significant weight loss, elevated serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin, increased histologic grade of cholangitis and number of T cells, macrophages, neutrophils and myofibroblasts per portal tract after 7 days. NKT cells were activated after intrabiliary injection of oxazolone with upregulation of activation markers. Cd1d-/- and wild-type mice pretreated with antibody blocking of CD1d were protected from disease. These findings implicate that cells in the bile ducts function as antigen-presenting cells in vivo and activate NKT cells in a CD1d-restricted manner. The elucidation of this biliary immune pathway opens up for potentially new therapeutic approaches for cholangiopathies.
Asunto(s)
Conductos Biliares/patología , Colangitis/inmunología , Células Epiteliales/inmunología , Células T Asesinas Naturales/inmunología , Animales , Anticuerpos Bloqueadores/administración & dosificación , Presentación de Antígeno , Antígenos CD1d/genética , Antígenos CD1d/inmunología , Antígenos CD1d/metabolismo , Células Cultivadas , Femenino , Humanos , Inmunización , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oxazolona/administración & dosificaciónRESUMEN
BACKGROUND: Pancreatoduodenectomy with superior mesenteric-portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high-volume centre, and to examine trends in management and outcome over a decade for the latter procedure. METHODS: This retrospective observational study included all patients undergoing pancreatoduodenectomy with or without venous resection at Oslo University Hospital between January 2006 and December 2015. Trends were evaluated by assessing preoperative clinical and radiological characteristics, as well as perioperative outcomes in three time intervals (early, intermediate and late). RESULTS: A total of 784 patients had a pancreatoduodenectomy, of whom 127 (16·2 per cent) underwent venous resection. Venous resection resulted in a longer operating time (median 422 versus 312 min; P = 0·001) and greater estimated blood loss (EBL) (median 700 versus 500 ml; P = 0·004) than standard pancreatoduodenectomy. The rate of severe complications was significantly higher for pancreatoduodenectomy with venous resection (37·0 versus 26·3 per cent; P = 0·014). The overall burden of complications, evaluated using the Comprehensive Complication Index (CCI), did not differ (median score 8·7 versus 8·7; P = 0·175). Trends in venous resection over time showed a significant reduction in EBL (median 1050 versus 375 ml; P = 0·001) and duration of hospital stay (median 14 versus 9 days; P = 0·011) between the early and late periods. However, despite an improvement in the intermediate period, severe complication rates returned to baseline in the late period (18 of 43 versus 9 of 42 versus 20 of 42 patients in early, intermediate and late periods respectively; P = 0·032), as did CCI scores (median 20·9 versus 0 versus 20·9; P = 0·041). CONCLUSION: Despite an initial improvement in severe complications for venous resection during pancreatoduodenectomy, this was not maintained over time. Every fourth patient with venous resection needed relaparotomy, most frequently for bleeding.
Asunto(s)
Venas Mesentéricas/cirugía , Pancreaticoduodenectomía , Vena Porta/cirugía , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Neoplasias del Conducto Colédoco/cirugía , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias , Reoperación/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on days 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin, which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.