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

文献类型： 外文期刊

第一作者： Gao, Hanchao

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

作者机构：

关键词： AKT;angiopoietin-1;angiopoietin-2;porcine iliac endothelial cells

期刊名称：XENOTRANSPLANTATION （ 影响因子：3.907； 五年影响因子：3.948 ）

ISSN： 0908-665X

年卷期： 2017 年 24 卷 4 期

页码：

收录情况： SCI

摘要： 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.

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