The In Vitro Protection of Human Decay Accelerating Factor and hDAF/Heme Oxygenase-1 Transgenes in Porcine Aortic Endothelial Cells Against Sera of Formosan Macaques

• Published in: Transplantation proceedings 2010-07, Vol.42 (6), p.2138-2141
• Main Authors: Tu, C.-F, Tai, H.-C, Wu, C.-P, Ho, L.-L, Lin, Y.-J, Hwang, C.-S, Yang, T.-S, Lee, J.-M, Tseng, Y.-L, Huang, C.-C, Weng, C.-N, Lee, P.-H
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Biological and medical sciences; CD55 Antigens - genetics; CD59 Antigens - genetics; Diseases of the skin. Cosmetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Knockout Techniques; Graft Rejection - prevention & control; Heme Oxygenase-1 - genetics; Humans; Kidney - physiology; Macaca - genetics; Macaca - immunology; Macaca - metabolism; Medical sciences; Papio; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Reverse Transcriptase Polymerase Chain Reaction; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Swine; Tissue, organ and graft immunology; Transgenes; Transplantation, Heterologous
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2010.05.104

Abstract To mitigate hyperacute rejection, pigs have been generated with α-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques ( Macaca cyclopis , MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF+ , hDAF+ /hHO-1+ , and hDAF+ /hHO-1− and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF+ /hHO-1+ showed no further protection against effects of MS on transgenic pAEC.