Over-expression of heme oxygenase-1 does not protect porcine endothelial cells from human xenoantibodies and complement-mediated lysis.
10.1007/s11596-013-1079-x
- Author:
Chi ZHANG
1
;
Lu WANG
;
Shan ZHONG
;
Xiao-xiao WANG
;
Ying XIANG
;
Shi CHEN
;
Gang CHEN
Author Information
1. Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China. odessues.zhang@gmail.com
- Publication Type:Journal Article
- MeSH:
Animals;
Antibodies, Heterophile;
immunology;
Cell Line;
Complement System Proteins;
immunology;
Dose-Response Relationship, Drug;
Endothelial Cells;
drug effects;
immunology;
Heme Oxygenase-1;
metabolism;
Humans;
Protoporphyrins;
pharmacology;
Swine;
Up-Regulation;
drug effects
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2013;33(1):102-106
- CountryChina
- Language:English
-
Abstract:
Accommodated organs can survive in the presence of anti-organ antibodies and complement. Heme oxygenase-1 (HO-1) is essential to ensure accommodation in concordant xenotransplant models. However, whether induction of HO-1 over-expression could protect porcine endothelial cells (PECs) against human xenoantibodies and complement-mediated lysis and induce an in vitro accommodation is still unknown. The SV40-immortalized porcine aorta-derived endothelial cell line (iPEC) was pre-incubated with 20, 50, or 80 μmol/L of cobalt-protoporphyrins IX (CoPPIX) for 24 h, and the HO-1 expression in iPECs was analyzed by using Western blotting. CoPPIX-treated or untreated iPECs were incubated with normal human AB sera, and complement-dependent cytotoxicity (CDC) was measured by both flow cytometry and lactate dehydrogenase (LDH) release assay. In vitro treatment with CoPPIX significantly increased the expression of HO-1 in iPECs in a dose-dependent manner. Over-expression of HO-1 was successfully achieved by incubation of iPECs with either 50 or 80 μmol/L of CoPPIX. However, HO-1 over-expression did not show any protective effects on iPECs against normal human sera-mediated cell lysis. In conclusion, induction of HO-1 over-expression alone is not enough to protect PECs from human xenoantibodies and complement-mediated humoral injury. Additionally, use of other protective strategies is needed to achieve accommodation in pig-to-primate xenotransplantation.
