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Tyrosine phosphorylation following lectin mediated endothelial cell stimulation
A Palmetshofer1, S C Robson, F H Bach
1Novartis Center for Immunobiology, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. palme@klin-biochem.uni-wuerzburg.de
Xenotransplantation
|December 16, 1998
Summary
Xenoreactive antibodies target various carbohydrate epitopes on endothelial cells, not just alpha-gal. Lectin binding to these glycans triggers endothelial cell activation and protein phosphorylation, crucial for understanding xenograft rejection.
Area of Science:
- Immunology
- Cell Biology
- Xenotransplantation Research
Background:
- Terminal alpha (1,3) galactosyl galactoside (alpha-gal) epitopes are key xenoreactive antigens in pig-to-primate xenotransplantation.
- Other carbohydrate epitopes can also be targeted by xenoreactive antibodies (XNA) in discordant xenotransplantation models.
Purpose of the Study:
- To investigate if lectin binding to various carbohydrate epitopes on endothelial cells induces similar activation and protein phosphorylation as alpha-gal.
- To identify potential minor xenoantigens or major xenoepitopes in different xenograft models.
Main Methods:
- Porcine aortic endothelial cells (PAEC) and human umbilical endothelial cells (HUVEC) were stimulated with various lectins.
- Lectins used included those binding to alpha-gal, sialic acid, mannose, N-acetylgalactosamine, and fucose.
- Protein phosphorylation, specifically of a 130 kDa protein (p130), was assessed.
Main Results:
- Binding of alpha-gal epitopes by Bandeiraea simplicifolia isolectin B4 (BS-IB4) induced PAEC activation and p130 phosphorylation.
- Lectins targeting sialic acid (SNA, MAA), mannose (ConA), and Wheat germ agglutinin (WGA) also induced p130 phosphorylation.
- Lectins for N-acetylgalactosamine (DOB, SOJ) and fucose (UEA-I) did not induce phosphorylation.
Conclusions:
- Endothelial cell activation occurs upon binding of diverse lectins to surface glycoprotein glycans.
- These carbohydrate epitopes, targeted by XNA, could represent minor xenoantigens or major xenoepitopes in xenotransplantation.
- XNA binding to these epitopes may contribute to xenograft rejection independently of complement activation.