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.
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Authors | 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 |
Journal | Xenotransplantation
(Xenotransplantation)
Vol. 24
Issue 4
(07 2017)
ISSN: 1399-3089 [Electronic] Denmark |
PMID | 28474373
(Publication Type: Journal Article)
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Copyright | © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
Chemical References |
- Angiopoietin-1
- Angiopoietin-2
- Immunoglobulins
- Protective Agents
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
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Topics |
- Angiopoietin-1
(metabolism)
- Angiopoietin-2
(metabolism)
- Animals
- Cells, Cultured
- Endothelial Cells
(drug effects, metabolism)
- Humans
- Ileum
(metabolism)
- Immunoglobulins
(metabolism)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Protective Agents
(pharmacology)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
- Swine
- Transplantation, Heterologous
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