title: Over-expression of heme oxygenase-1 does not protect porcine endothelial cells from human xenoantibodies and complement-mediated lysis.
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.
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Urology, Fujian Provincial Hospital, Fujian, 350001, China.
authors: Chi
authors: C
authors: Zhang
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors: Lu
authors: L
authors: Wang
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors: Shan
authors: S
authors: Zhong
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors: Xiao-Xiao
authors: XX
authors: Wang
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors: Ying
authors: Y
authors: Xiang
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China.|Key Laboratory of Organ Transplantation, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.|Key Laboratory of Organ Transplantation, Ministry of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors: Shi
authors: S
authors: Chen
authors: Institute of Organ Transplantation, Huazhong University of Science and Technology, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn.|Key Laboratory of Organ Transplantation, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn.|Key Laboratory of Organ Transplantation, Ministry of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn.
authors: Gang
authors: G
authors: Chen
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D011524:Protoporphyrins / Q000494:pharmacology*; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000910:Antibodies, Heterophile; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D003165:Complement System Proteins; D051547:Heme Oxygenase-1
references: J Immunol. 2001 Mar 15;166(6):4185-94
references: 11238670
references: Transpl Immunol. 2005 Aug;14(3-4):159-69
references: 15982558
references: Liver Transpl. 2003 Jan;9(1):22-30
references: 12514769
references: Blood. 2005 Sep 1;106(5):1694-702
references: 15920011
references: Transplant Proc. 1996 Apr;28(2):535
references: 8623251
references: Nat Med. 2001 Jun;7(6):693-8
references: 11385506
references: Am J Transplant. 2001 Sep;1(3):260-9
references: 12102260
references: Nat Med. 1998 Sep;4(9):1073-7
references: 9734404
references: Transplantation. 2006 Jan 27;81(2):273-83
references: 16436972
references: Am J Transplant. 2004 Jul;4(7):1089-96
references: 15196066
references: Immunol Today. 1999 Oct;20(10):434-7
references: 10500288
references: Transplantation. 2002 Aug 15;74(3):334-45
references: 12177611
references: Transplant Proc. 2010 Jul-Aug;42(6):2138-41
references: 20692427
references: Transplantation. 1996 Oct 27;62(8):1127-36
references: 8900314
references: Blood. 2009 Feb 12;113(7):1598-607
references: 19036700
references: Transpl Immunol. 2008 Jul;19(3-4):202-8
references: 18598766