Expression of human alpha-galactosidase and alpha1,2-fucosyltransferase genes modifies the cell surface Galalpha1,3Gal antigen and confers resistance to human serum-mediated cytolysis.
Chin Med Sci J
; 19(1): 31-7, 2004 Mar.
Article
em En
| MEDLINE
| ID: mdl-15104222
ABSTRACT
OBJECTIVE:
To explore the strategies which reduce the amount of xenoantigen Galalpha1,3Gal.METHODS:
Human alpha-galactosidase gene and alpha1,2-fucosyltransferase gene were transferred into cultured porcine vascular endothelial cells PEDSV.15 and human alpha-galactosidase transgenic mice were produced. The Galalpha1,3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed.RESULTS:
Human alpha-galactosidase gene alone reduced 78% of Galalpha1,3Gal on PEDSV.15 cell surface while human alpha-galactosidase combined with alpha1,2-fucosyltransferase genes removed Galalpha1,3Gal completely. Decrease of Galalpha1,3Gal could reduce susceptibility of cells to human antibody-mediated lysis, especially during co-expression of alpha-galactosidase gene and alpha1,2-fucosyltransferase gene. RT-PCR indicated positive human alpha-galactosidase gene expression in all organs of positive human alpha-galactosidase transgenic F1 mice including heart, liver, kidney, lung, and spleen, the amount of Galalpha1,3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by complement-mediated lysis compared with 24% of those from normal mice.CONCLUSIONS:
Human alpha-galactosidase gene and alpha1,2-fucosyltransferase gene effectively reduce the expression of Galalpha1,3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human alpha-galactosidase in mice can also eliminate the Galalpha1,3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos Heterófilos
/
Alfa-Galactosidase
/
Dissacarídeos
/
Fucosiltransferases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Chin Med Sci J
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2004
Tipo de documento:
Article