Delta-short consensus repeat 4-decay accelerating factor (DAF: CD55) inhibits complement-mediated cytolysis but not NK cell-mediated cytolysis.
NK cells play a critical role in the rejection of xenografts. In this study, we report on an investigation of the effect of complement regulatory protein, a decay accelerating factor (DAF: CD55), in particular, on NK cell-mediated cytolysis. Amelioration of human NK cell-mediated pig endothelial cell (PEC) and pig fibroblast cell lyses by various deletion mutants and point substitutions of DAF was tested, and compared with their complement regulatory function. Although wild-type DAF and the delta-short consensus repeat (SCR) 1-DAF showed clear inhibition of both complement-mediated and NK-mediated PEC lyses, delta-SCR2-DAF and delta-SCR3-DAF failed to suppress either process. However, delta-SCR4-DAF showed a clear complement regulatory effect, but had no effect on NK cells. Conversely, the point substitution of DAF (L147 x F148 to SS and KKK(125-127) to TTT) was half down-regulated in complement inhibitory function, but the inhibition of NK-mediated PEC lysis remained unchanged. Other complement regulatory proteins, such as the cell membrane-bound form factor H, fH-PI, and C1-inactivator, C1-INH-PI, and CD59 were also assessed, but no suppressive effect on NK cell-mediated PEC lysis was found. These data suggest, for DAF to function on NK cells, SCR2-4 is required but no relation to its complement regulatory function exists.
Miyagawa
Shuji
S
Department of Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. orgtrp.med.osaka-u.ac.jp
Kubo
Tomoko
T
Matsunami
Katsuyoshi
K
Kusama
Tamiko
T
Beppu
Keiko
K
Nozaki
Hiroshi
H
Moritan
Toshiyuki
T
Ahn
Curie
C
Kim
Jae Young
JY
Fukuta
Daisuke
D
Shirakura
Ryota
R
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D018958:CD55 Antigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002860:Chromium Radioisotopes / Q000378:metabolism; D003167:Complement Activation / Q000235:genetics; D003169:Complement Inactivator Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016384:Consensus Sequence / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D017384:Sequence Deletion; D013552:Swine; D014162:Transfection
D018958:CD55 Antigens; D002860:Chromium Radioisotopes; D003169:Complement Inactivator Proteins; D007371:Interferon-gamma