title: Inhibition of human complement-dependent cell lysis by bovine aortic endothelial cells transfected with membrane-bound complement-regulatory factor (DAF and HRF20) gene using a retroviral vector.
abstract: The endothelial cells (EC) of xenografts are the target of hyperacute rejection induced by complement activation via the classical and/or the alternative pathway. To protect these cells from the attack of human complement, decay-accelerating factor (DAF, CD55) and homologous restriction factor 20 (HRF20, CD59), which belong to human complement regulatory factors, were transfected into bovine aortic EC (BAEC) using retroviral vector. Cell surface expression of DAF and HRF20 on BAEC transfectants (BAEC/DAF, BAEC/HRF20) is comparable to that on human umbilical vein EC. Phosphatidyl inositol-phospholipase C treatment diminished or abolished cell surface expression of DAF and HRF20 on BAEC. The addition of human serum to BAEC led to complement-dependent cell lysis, whereas practically no lysis was observed after addition of human serum to BAEC/DAF and BAEC/HRF20. The addition of human serum plus rabbit complement to BAEC/DAF and BAEC/HRF20 caused complement-dependent cell lysis that was comparable to that observed for BAEC. These data demonstrate that xenograft EC transfected with DAF or HRF20 cDNA using retroviral vector are protected from complement-dependent cell lysis.
authors.affiliation: Department of Surgery II, Nagoya University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Isobe
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.forename: I
authors.initials: I
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: I
authors.initials: I
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Takagi
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000502:physiology*; D018957:CD59 Antigens / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D003165:Complement System Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors; D006801:Humans; D011817:Rabbits; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D003165:Complement System Proteins