Back to Search
Start Over
Porcine Extrahepatic Vascular Endothelial Asialoglycoprotein Receptor 1 Mediates Xenogeneic Platelet Phagocytosis In Vitro and in Human-to-Pig Ex Vivo Xenoperfusion
- Source :
- Transplantation, Transplantation, Vol. 99, No 4 (2015) pp. 693-701, 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
- Publication Year :
- 2015
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2015.
-
Abstract
- 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 {\textpm} 33 at beginning to 13 {\textpm} 6 {\texttimes} 10/µL (P < 0.0001) after 10 minutes of perfusion whereas no significant decrease of platelets was seen during autologous perfusions (171 {\textpm} 26 to 122 {\textpm} 95 {\texttimes} 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.
- Subjects :
- Blood Platelets
Asialoglycoprotein Receptor/immunology/metabolism
Male
Time Factors
Swine
Xenotransplantation
medicine.medical_treatment
Phagocytosis
Transplantation, Heterologous
610 Medicine & health
Asialoglycoprotein Receptor
Biology
Amputation, Surgical
Blood cell
Andrology
Platelet Adhesiveness
Species Specificity
Platelet adhesiveness
Forelimb
Forelimb/blood supply/surgery
medicine
Animals
Humans
Blood Transfusion
Platelet
Thrombocytopenia/blood/immunology
Amputation
Cells, Cultured
ddc:616
Transplantation
Blood Platelets/immunology/metabolism
Asialoglycoprotein
Endothelial Cells
Thrombocytopenia
3. Good health
medicine.anatomical_structure
Blood Transfusion/methods
Models, Animal
Immunology
Female
Asialoglycoprotein receptor
Endothelial Cells/immunology/metabolism
Ex vivo
Signal Transduction
Subjects
Details
- ISSN :
- 00411337
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....df90ad20c1918216a15d12dd6d368071