Objective To explore the strategies which reduce the amount of xenoantigen Galα1, 3 Gal. Methods Human α-galactosidase gene and α1,2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothel...Objective To explore the strategies which reduce the amount of xenoantigen Galα1, 3 Gal. Methods Human α-galactosidase gene and α1,2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothelial cells PEDSV.15 and human α-galactosidase transgenic mice were produced. The Galα1,3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed. Results Human α-galactosidase gene alone reduced 78% of Galα1,3Gal on PEDSV.15 cell surface while human α-galactosidase combined with α1,2-fucosyltransferase genes removed Galα1,3Gal completely. Decrease of Galα1,3Gal could reduce susceptibility of cells to human antibody-mediated lysis, especially during co-expression of α-galactosidase gene and α1,2-fucosyltransferase gene. RT-PCR indicated positive human α-galactosidase gene expression in all organs of positive human α-galacto-sidase transgenic F1 mice including heart, liver, kidney, lung, and spleen, the amount of Galα1,3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by comp-lement-mediated lysis compared with 24% of those from normal mice. Conclusions Human α-galactosidase gene and α1,2-fucosyltransferase gene effectively reduce the expression of Galα1,3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human α-galactosidase in mice can also eliminate the Galα1,3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.展开更多
The molecular coating on the surface of microvascular endothelium has been identified as a barrier to transvascular exchange of solutes. With a thickness of hundreds of nanometers, this endothelial surface layer （ESL...The molecular coating on the surface of microvascular endothelium has been identified as a barrier to transvascular exchange of solutes. With a thickness of hundreds of nanometers, this endothelial surface layer （ESL） has been treated as a porous do- main within which fluid shear stresses are dissipated and transmitted to the solid matrix to initiate mechanotransduction events. The present study aims to examine the effects of the ESL thickness and permeability on the transmission of shear stress throughout the ESL. Our results indicate that fluid shear stresses rapidly decrease to insignificant levels within a thin transition layer near the outer boundary of the ESL with a thickness on the order of ten nanometers. The thickness of the transition zone between free fluid and the porous layer was found to be proportional to the square root of the Darcy permeability. As the per- meability is reduced ten-fold, the interfacial fluid and solid matrix shear stress gradients increase exponentially two-fold. While the interracial fluid shear stress is positively related to the ESL thickness, the transmitted matrix stress is reduced by about 50% as the ESL thickness is decreased from 500 to 100 nm, which may occur under pathological conditions. Thus, thickness and permeability of the ESL are two main factors that determine flow features and the apportionment of shear stress- es between the fluid and solid phases of the ESL. These results may shed light on the mechanisms of force transmission through the ESL and the pathological events caused by alterations in thickness and permeability of the ESL.展开更多
The author studies the L2 gradient flow of the Helfrich functional, which is a functional describing the shapes of human red blood cells. For any λi ≥ 0 and co, the author obtains a lower bound on the lifespan of th...The author studies the L2 gradient flow of the Helfrich functional, which is a functional describing the shapes of human red blood cells. For any λi ≥ 0 and co, the author obtains a lower bound on the lifespan of the smooth solution, which depends only on the concentration of curvature for the initial surface.展开更多
文摘Objective To explore the strategies which reduce the amount of xenoantigen Galα1, 3 Gal. Methods Human α-galactosidase gene and α1,2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothelial cells PEDSV.15 and human α-galactosidase transgenic mice were produced. The Galα1,3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed. Results Human α-galactosidase gene alone reduced 78% of Galα1,3Gal on PEDSV.15 cell surface while human α-galactosidase combined with α1,2-fucosyltransferase genes removed Galα1,3Gal completely. Decrease of Galα1,3Gal could reduce susceptibility of cells to human antibody-mediated lysis, especially during co-expression of α-galactosidase gene and α1,2-fucosyltransferase gene. RT-PCR indicated positive human α-galactosidase gene expression in all organs of positive human α-galacto-sidase transgenic F1 mice including heart, liver, kidney, lung, and spleen, the amount of Galα1,3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by comp-lement-mediated lysis compared with 24% of those from normal mice. Conclusions Human α-galactosidase gene and α1,2-fucosyltransferase gene effectively reduce the expression of Galα1,3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human α-galactosidase in mice can also eliminate the Galα1,3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.
基金supported by the National Basic Research Program of China(Grant No.2012CB934101)the National Natural Science Foundation of China(Grant Nos.51175282 and 51375254)
文摘The molecular coating on the surface of microvascular endothelium has been identified as a barrier to transvascular exchange of solutes. With a thickness of hundreds of nanometers, this endothelial surface layer （ESL） has been treated as a porous do- main within which fluid shear stresses are dissipated and transmitted to the solid matrix to initiate mechanotransduction events. The present study aims to examine the effects of the ESL thickness and permeability on the transmission of shear stress throughout the ESL. Our results indicate that fluid shear stresses rapidly decrease to insignificant levels within a thin transition layer near the outer boundary of the ESL with a thickness on the order of ten nanometers. The thickness of the transition zone between free fluid and the porous layer was found to be proportional to the square root of the Darcy permeability. As the per- meability is reduced ten-fold, the interfacial fluid and solid matrix shear stress gradients increase exponentially two-fold. While the interracial fluid shear stress is positively related to the ESL thickness, the transmitted matrix stress is reduced by about 50% as the ESL thickness is decreased from 500 to 100 nm, which may occur under pathological conditions. Thus, thickness and permeability of the ESL are two main factors that determine flow features and the apportionment of shear stress- es between the fluid and solid phases of the ESL. These results may shed light on the mechanisms of force transmission through the ESL and the pathological events caused by alterations in thickness and permeability of the ESL.
基金Project supported by the National Natural Science Foundation of China(No.11026121)the TrainingProgramme Foundation for the Excellent Talents of Beijing(No.2012D005003000004)
文摘The author studies the L2 gradient flow of the Helfrich functional, which is a functional describing the shapes of human red blood cells. For any λi ≥ 0 and co, the author obtains a lower bound on the lifespan of the smooth solution, which depends only on the concentration of curvature for the initial surface.
