Porcine extrahepatic vascular endothelial asialoglycoprotein receptor 1 mediates xenogeneic platelet phagocytosis in vitro and in human-to-pig ex vivo xenoperfusion.


Autoria(s): Bongoni, Anjan K; Kiermeir, David; Denoyelle, Julie Sophie Cécile; Jenni, Hansjörg; Burlak, Christopher; Seebach, Jörg D; Vögelin, Esther; Constantinescu, Mihai Adrian; Rieben, Robert
Data(s)

01/04/2015

Resumo

BACKGROUND Asialoglycoprotein receptor-1 (ASGR1) mediates capture and phagocytosis of platelets in pig-to-primate liver xenotransplantation. However, thrombocytopenia is also observed in xenotransplantation or xenoperfusion of other porcine organs than liver. We therefore assessed ASGR1 expression as well as ASGR1-mediated xenogeneic platelet phagocytosis in vitro and ex vivo on porcine aortic, femoral arterial, and liver sinusoidal endothelial cells (PAEC/PFAEC/PLSEC). METHODS Porcine forelimbs were perfused with whole, heparinized human or autologous pig blood. Platelets were counted at regular intervals. Pig limb muscle and liver, as well as PAEC/PFAEC/PLSEC, were characterized for ASGR1 expression. In vitro, PAEC cultured on microcarrier beads and incubated with non-anticoagulated human blood were used to study binding of human platelets and platelet-white blood cell aggregation. Carboxyfluorescein diacetate succinimidyl ester-labeled human platelets were exposed to PAEC/PFAEC/PLSEC and analyzed for ASGR1-mediated phagocytosis. RESULTS Human platelet numbers decreased from 102 ± 33 at beginning to 13 ± 6 × 10/μL (P < 0.0001) after 10 minutes of perfusion, whereas no significant decrease of platelets was seen during autologous perfusions (171 ± 26 to 122 ± 95 × 10/μL). The PAEC, PFAEC, and PLSEC all showed similar ASGR1 expression. In vitro, no correlation was found between reduction in platelet count and platelet-white blood cell aggregation. Phagocytosis of human carboxyfluorescein diacetate succinimidyl ester-labeled platelets by PAEC/PFAEC/PLSEC peaked at 15 minutes and was inhibited (P < 0.05 to P < 0.0001) by rabbit anti-ASGR1 antibody and asialofetuin. CONCLUSIONS The ASGR1 expressed on aortic and limb arterial pig vascular endothelium plays a role in binding and phagocytosis of human platelets. Therefore, ASGR1 may represent a novel therapeutic target to overcome thrombocytopenia associated with vascularized pig-to-primate xenotransplantation.

Formato

application/pdf

Identificador

http://boris.unibe.ch/69607/1/00007890-201504000-00012.pdf

Bongoni, Anjan K; Kiermeir, David; Denoyelle, Julie Sophie Cécile; Jenni, Hansjörg; Burlak, Christopher; Seebach, Jörg D; Vögelin, Esther; Constantinescu, Mihai Adrian; Rieben, Robert (2015). Porcine extrahepatic vascular endothelial asialoglycoprotein receptor 1 mediates xenogeneic platelet phagocytosis in vitro and in human-to-pig ex vivo xenoperfusion. Transplantation, 99(4), pp. 693-701. Lippincott Williams & Wilkins 10.1097/TP.0000000000000553 <http://dx.doi.org/10.1097/TP.0000000000000553>

doi:10.7892/boris.69607

info:doi:10.1097/TP.0000000000000553

info:pmid:25675194

urn:issn:0041-1337

Idioma(s)

eng

Publicador

Lippincott Williams & Wilkins

Relação

http://boris.unibe.ch/69607/

Direitos

info:eu-repo/semantics/openAccess

Fonte

Bongoni, Anjan K; Kiermeir, David; Denoyelle, Julie Sophie Cécile; Jenni, Hansjörg; Burlak, Christopher; Seebach, Jörg D; Vögelin, Esther; Constantinescu, Mihai Adrian; Rieben, Robert (2015). Porcine extrahepatic vascular endothelial asialoglycoprotein receptor 1 mediates xenogeneic platelet phagocytosis in vitro and in human-to-pig ex vivo xenoperfusion. Transplantation, 99(4), pp. 693-701. Lippincott Williams & Wilkins 10.1097/TP.0000000000000553 <http://dx.doi.org/10.1097/TP.0000000000000553>

Palavras-Chave #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed