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Tacrolimus prevents von Willebrand factor secretion by allostimulated human glomerular endothelium.
Béland, S; Désy, O; Ung, R V; Vallin, P; Latulippe, E; Riopel, J; De Serres, S A.
Afiliación
  • Béland S; Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
  • Désy O; Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
  • Ung RV; Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
  • Vallin P; Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
  • Latulippe E; Department of Pathology, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
  • Riopel J; Department of Pathology, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
  • De Serres SA; Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada.
Am J Transplant ; 18(9): 2314-2321, 2018 09.
Article en En | MEDLINE | ID: mdl-29790290
Little is known about the endothelial injury caused directly by circulating donor-specific antibodies (DSAs) during antibody-mediated rejection. von Willebrand factor (vWF) is a highly thrombotic glycoprotein stored in Weibel-Palade bodies in endothelial cells. It has been shown that its secretion is triggered by allostimulation. Calcineurin-like phosphatases regulate pathways involved in vWF secretion. Therefore, we hypothesized that tacrolimus would prevent alloantibody-induced glomerular lesions, in part via inhibition of vWF secretion from endothelial cells. Here, we used a human in vitro model of glomerular endothelium expressing HLA class I and II antigens and demonstrated that anti-HLA class II antibodies elicit a higher endothelial release of vWF than do anti-HLA class I antibodies in cell supernatants. We observed that tacrolimus treatment decreased vWF secretion after stimulation with both classes of anti-HLA antibodies and decreased platelet adhesion on allostimulated endothelial cells in a microfluidic chamber. In kidney recipients, tacrolimus trough levels were negatively associated with vWF blood levels. These results indicate that direct disruption of hemostasis via vWF secretion is a potential mechanism of antibody-mediated injury in patients with DSAs. Our results further suggest that the targeting of microcirculation hemostasis may be beneficial to prevent the development of microangiopathic lesions in antibody-mediated rejection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de von Willebrand / Endotelio Vascular / Trasplante de Riñón / Tacrolimus / Rechazo de Injerto / Isoanticuerpos / Glomérulos Renales Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de von Willebrand / Endotelio Vascular / Trasplante de Riñón / Tacrolimus / Rechazo de Injerto / Isoanticuerpos / Glomérulos Renales Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos