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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 Antibody-Mediated Complement-Dependent Cytotoxicity Through Phosphatidylinositide 3-kinase/AKT Pathway Activation

Hanchao Gao, Pengfei Chen, Ling Wei, Jia Xu, Lu Liu, Yanli Zhao, Hidetaka Hara, Dengke Pan, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou

Xenotransplantation. 2017 Jul;24(4).

PMID: 28474373

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248741	Angiopoietin-1 human			Price

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