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 / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
;
(4): 31-37, 2004.
Article
in English
| WPRIM
| ID: wpr-254032
ABSTRACT
<p><b>OBJECTIVE</b>To explore the strategies which reduce the amount of xenoantigen Galalpha1,3Gal.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Spleen
/
Swine
/
Mice, Transgenic
/
Transfection
/
Cells, Cultured
/
Antigens, Heterophile
/
Cell Death
/
Alpha-Galactosidase
/
Cell Biology
/
Endothelial Cells
Limits:
Animals
/
Humans
Language:
English
Journal:
Chinese Medical Sciences Journal
Year:
2004
Type:
Article
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