BACKGROUND: Abnormal adhesion of red blood cells (RBCs) to vascular endothelium is often associated with reduced levels of sialic acids on RBC membranes and with elevated levels of pro-adhesive plasma proteins. However, the synergistic effects of these two factors on the adhesion are not clear. In this work, we tested the hypothesis that macromolecular depletion interaction originating from non-adsorbing macromolecules can promote the adhesion of RBCs with reduced sialic acid content to the endothelium. METHODS: RBCs are treated with neuraminidase to specifically remove sialic acids from their surface followed by the evaluation of their deformability, zeta potential and membrane proteins. The adhesion of these enzyme-treated RBCs to cultured human umbilical vein endothelial cells (ECs) is studied in the presence of 70 or 500kDa dextran with a flow chamber assay. RESULTS: Our results demonstrate that removal of sialic acids from RBC surface can induce erythrocyte adhesion to endothelial cells and that such adhesion is significantly enhanced in the presence of high-molecular weight dextran. The adhesion-promoting effect of dextran exhibits a strong dependence on dextran concentration and molecular mass, and it is concluded to originate from macromolecular depletion interaction. CONCLUSION: These results suggest that elevated levels of non-adsorbing macromolecules in plasma might play a significant role in promoting endothelial adhesion of erythrocytes with reduced sialic acids. GENERAL SIGNIFICANCE: Our findings should therefore be of great value in understanding abnormal RBC-EC interactions in pathophysiological conditions (e.g., sickle cell disease and diabetes) and after blood transfusions.
BACKGROUND: Abnormal adhesion of red blood cells (RBCs) to vascular endothelium is often associated with reduced levels of sialic acids on RBC membranes and with elevated levels of pro-adhesive plasma proteins. However, the synergistic effects of these two factors on the adhesion are not clear. In this work, we tested the hypothesis that macromolecular depletion interaction originating from non-adsorbing macromolecules can promote the adhesion of RBCs with reduced sialic acid content to the endothelium. METHODS: RBCs are treated with neuraminidase to specifically remove sialic acids from their surface followed by the evaluation of their deformability, zeta potential and membrane proteins. The adhesion of these enzyme-treated RBCs to cultured human umbilical vein endothelial cells (ECs) is studied in the presence of 70 or 500kDa dextran with a flow chamber assay. RESULTS: Our results demonstrate that removal of sialic acids from RBC surface can induce erythrocyte adhesion to endothelial cells and that such adhesion is significantly enhanced in the presence of high-molecular weight dextran. The adhesion-promoting effect of dextran exhibits a strong dependence on dextran concentration and molecular mass, and it is concluded to originate from macromolecular depletion interaction. CONCLUSION: These results suggest that elevated levels of non-adsorbing macromolecules in plasma might play a significant role in promoting endothelial adhesion of erythrocytes with reduced sialic acids. GENERAL SIGNIFICANCE: Our findings should therefore be of great value in understanding abnormal RBC-EC interactions in pathophysiological conditions (e.g., sickle cell disease and diabetes) and after blood transfusions.
Authors: Zachary M Kiser; Anel Lizcano; Julia Nguyen; Greta L Becker; John D Belcher; Ajit P Varki; Gregory M Vercellotti Journal: Blood Cells Mol Dis Date: 2019-12-20 Impact factor: 3.039
Authors: Rudy Chang; Juan Castillo; Alexander C Zambon; Tatiana B Krasieva; Mark J Fisher; Rachita K Sumbria Journal: Front Cell Neurosci Date: 2018-09-06 Impact factor: 5.505