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Angiopoietin‐1 and angiopoietin‐2 protect porcine iliac endothelial cells from human antibody‐mediated complement‐dependent cytotoxicity through phosphatidylinositide 3‐kinase/AKT pathway activation

Angiopoietin‐1 and angiopoietin‐2 protect porcine iliac endothelial cells from human... Cytokines play crucial roles in inflammation, but their role in xenotransplantation remains elusive. We assessed the role of several cytokines using an in vitro model of human antibody‐mediated complement‐dependent cytotoxicity (CDC). Recombinant human angiopoietin‐1 (Ang‐1) protected porcine iliac endothelial cells (PIECs) from human antibody‐mediated CDC. Interestingly, human angiopoietin‐2 (Ang‐2) had a similar protective effect on PIECs. By flow cytometry analysis, the extent of human IgM and IgG binding to PIECs did not decrease when PIECs were exposed to Ang‐1/Ang‐2. The mRNA level of complement regulators (CD46, CD55, CD59) was not upregulated in PIECs treated with Ang‐1/Ang‐2, both of which activated the PI3K/AKT pathway in PIECs. Wortmannin, which inhibits phosphatidylinositide 3‐kinase (PI3K), suppressed Ang‐1/Ang‐2‐induced AKT phosphorylation and consequent Ang‐1/Ang‐2‐mediated protection of PIECs in human antibody‐mediated CDC model. Moreover, dominant negative AKT also suppressed Ang‐1/Ang‐2‐mediated protection of PIECs in this model. In conclusion, our data suggest that human Ang‐1/Ang‐2 induces the protection of PIECs from human antibody‐mediated CDC by activating the PI3K/AKT pathway. Ang‐1/Ang‐2 is likely to protect porcine endothelial cells and may be beneficial in xenotransplantation research. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Xenotransplantation Wiley

Angiopoietin‐1 and angiopoietin‐2 protect porcine iliac endothelial cells from human antibody‐mediated complement‐dependent cytotoxicity through phosphatidylinositide 3‐kinase/AKT pathway activation

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References (32)

Publisher
Wiley
Copyright
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
ISSN
0908-665X
eISSN
1399-3089
DOI
10.1111/xen.12309
pmid
28474373
Publisher site
See Article on Publisher Site

Abstract

Cytokines play crucial roles in inflammation, but their role in xenotransplantation remains elusive. We assessed the role of several cytokines using an in vitro model of human antibody‐mediated complement‐dependent cytotoxicity (CDC). Recombinant human angiopoietin‐1 (Ang‐1) protected porcine iliac endothelial cells (PIECs) from human antibody‐mediated CDC. Interestingly, human angiopoietin‐2 (Ang‐2) had a similar protective effect on PIECs. By flow cytometry analysis, the extent of human IgM and IgG binding to PIECs did not decrease when PIECs were exposed to Ang‐1/Ang‐2. The mRNA level of complement regulators (CD46, CD55, CD59) was not upregulated in PIECs treated with Ang‐1/Ang‐2, both of which activated the PI3K/AKT pathway in PIECs. Wortmannin, which inhibits phosphatidylinositide 3‐kinase (PI3K), suppressed Ang‐1/Ang‐2‐induced AKT phosphorylation and consequent Ang‐1/Ang‐2‐mediated protection of PIECs in human antibody‐mediated CDC model. Moreover, dominant negative AKT also suppressed Ang‐1/Ang‐2‐mediated protection of PIECs in this model. In conclusion, our data suggest that human Ang‐1/Ang‐2 induces the protection of PIECs from human antibody‐mediated CDC by activating the PI3K/AKT pathway. Ang‐1/Ang‐2 is likely to protect porcine endothelial cells and may be beneficial in xenotransplantation research.

Journal

Xenotransplantation – Wiley

Published: Jul 1, 2017

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