Poloxamer 188 reduces normal and phosphatidylserine-exposing erythrocyte adhesion to endothelial cells in dextran solutions

Abstract

Abnormal red blood cell (RBC) adhesion to endothelial cells (ECs) has been correlated with vascular complications in diseases such as sickle cell anemia and diabetes. Poloxamer 188 (P188) has been clinically tested to treat vaso-occlusion. However, the underlying mechanism(s) have not been clarified, making a methodical application difficult. In this study, we investigate how and to what extent P188 reduces RBC adhesion to ECs in plasma-like solutions. RBC adhesion to ECs is studied in solutions containing dextran, which is known to induce adhesion via macromolecular depletion interaction. It is demonstrated that P188 itself does not induce adhesion of normal RBCs to ECs but significantly reduces the adhesion in solutions containing high molecular mass-dextran. In addition, it is shown that P188 can reduce the adhesion of RBCs with enhanced exposure of phosphatidylserine (PS). Measurements of the electrophoretic mobility indicate that P188 increases the local viscosity inside the electric double layer of RBCs. Based on these results this study suggests that P188 reduces macromolecular depletion interaction, via penetrating into the depletion layer. Taking into consideration that dextran mimics the effects of pro-adhesive non-adsorbing plasma proteins and macromolecules, our study therefore suggests a mechanism for the adhesion reducing effect of P188 and should thus be of potential value for a detailed understanding of how cell–cell interactions in pathological conditions can be reduced.