Article

Journal of Huazhong University of Science and Technology [Medical Sciences]

, Volume 33, Issue 1, pp 102-106

First online:

Over-expression of heme oxygenase-1 does not protect porcine endothelial cells from human xenoantibodies and complement-mediated lysis

  • Chi Zhang张 弛Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and TechnologyDepartment of Urology, Fujian Provincial Hospital
  • , Lu Wang王 璐Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and Technology
  • , Shan Zhong钟 山Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and Technology
  • , Xiao-xiao Wang王筱啸Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and Technology
  • , Ying Xiang向 莹Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and Technology
  • , Shi Chen陈 实Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and TechnologyKey Laboratory of Organ Transplantation, Ministry of Education, Huazhong University of Science and TechnologyKey Laboratory of Organ Transplantation, Ministry of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Gang Chen陈 刚Affiliated withInstitute of Organ Transplantation, Huazhong University of Science and TechnologyKey Laboratory of Organ Transplantation, Ministry of Education, Huazhong University of Science and TechnologyKey Laboratory of Organ Transplantation, Ministry of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Email author 

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Summary

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.

Key words

heme oxygenase-1 porcine endothelial cells complement-dependent cytotoxicity xenotransplantation