C5b-8 step lysis of swine endothelial cells by human complement and functional feature of transfected CD59.
The authors established several swine endothelial cell (SEC) lines expressing human CD59 by transfection of cDNA, and assessed the function of the transfectant molecules in comparison with those of membrane cofactor protein (MCP) and decay-accelerating factor (DAF) in an in vitro hyperacute rejection model of swine to human discordant xenograft. At the usual expression rate, DAF and MCP protected SEC from human complement mediated cell lysis, but CD59 did not block human complement attack on SEC. However, CD59 protects SEC from cell lysis when sufficiently expressed as in human umbilical vein (HUVEC). The authors examined why CD59 needed so many molecules to protect human complement-mediated SEC lysis and found that SEC underwent lysis by human C5b-8. The degree of C5b-8 step lysis of SEC was approximately 70% of the total activation (C5b-9). Additionally, CD59 protected human complement activities less efficiently at the C5b-8 step than at the C9-step. Therefore, to overcome human complement mediated SEC lysis, C8 activity must be inhibited by dense expression of CD59.
Miyagawa
S
S
Division of Organ Transplantation, Biomedical Research Center, Osaka University Medical School, Japan.
Mikata
S
S
Shirakura
R
R
Matsuda
H
H
Nagasawa
S
S
Terados
A
A
Hatanaka
M
M
Matsumoto
M
M
Seya
T
T
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D018958:CD55 Antigens / Q000096:biosynthesis / Q000502:physiology; D018957:CD59 Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D003169:Complement Inactivator Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D003165:Complement System Proteins / Q000276:immunology* / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D013552:Swine; D014162:Transfection / Q000276:immunology*
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; C042295:complement C5b-8 complex; D003165:Complement System Proteins