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

, Volume 33, Issue 1, pp 102–106

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

  • Chi Zhang张 弛
  • Lu Wang王 璐
  • Shan Zhong钟 山
  • Xiao-xiao Wang王筱啸
  • Ying Xiang向 莹
  • Shi Chen陈 实
  • Gang Chen陈 刚
Article

DOI: 10.1007/s11596-013-1079-x

Cite this article as:
Zhang, C., Wang, L., Zhong, S. et al. J. Huazhong Univ. Sci. Technol. [Med. Sci.] (2013) 33: 102. doi:10.1007/s11596-013-1079-x

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-1porcine endothelial cellscomplement-dependent cytotoxicityxenotransplantation

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Chi Zhang张 弛
    • 1
    • 4
  • Lu Wang王 璐
    • 1
  • Shan Zhong钟 山
    • 1
  • Xiao-xiao Wang王筱啸
    • 1
  • Ying Xiang向 莹
    • 1
  • Shi Chen陈 实
    • 1
    • 2
    • 3
  • Gang Chen陈 刚
    • 1
    • 2
    • 3
  1. 1.Institute of Organ TransplantationHuazhong University of Science and TechnologyWuhanChina
  2. 2.Key Laboratory of Organ Transplantation, Ministry of EducationHuazhong University of Science and TechnologyWuhanChina
  3. 3.Key Laboratory of Organ Transplantation, Ministry of Public Health, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  4. 4.Department of UrologyFujian Provincial HospitalFujianChina