Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior

The abnormal adherence of sickle red blood cells (SS RBC) to vascular endot helium may play an important role in vasoocclusion in sickle cell anemia, T hrombospondin (TSP), unusually large molecular weight forms of von Willebra nd factor, and laminin are known to enhance adhesion of SS RBC. Also, these endothelial proteins bind to sulfated glycolipids and this binding is inhi bited by anionic polysaccharides, Reversible sickling may expose normally c ryptic membrane sulfatides that could mediate this adhesive interaction. In this study, we have investigated the effect of anionic polysaccharides, in the presence or absence of TSP, on SS RBC adhesion to the endothelium, usi ng cultured human umbilical Vein endothelial cells (HUVEC) (for the adhesio n assay) and the ex vivo mesocecum of the rat (for hemodynamic evaluation). The baseline adhesion lie, without added TSP) of SS RBC to HUVEC was most effectively inhibited by high molecular weight dextran sulfate (HDS), where as low molecular weight dextran sulfate (LDS) and the glycosaminoglycan cho ndroitin sulfate A (CSA) also had significant inhibitory effects. Heparin w as mildly effective whereas other glycosaminoglycans (chondroitin sulfates B and C, heparan sulfate, end fucoidan) were ineffective. Similarly, HDS an d CSA resulted in an improved hemodynamic: behavior of SS RBC. Soluble TSP caused significant increases in SS RBC adhesion and in the peripheral resis tance. Both HDS and CSA prevented TSP-enhanced adhesion and hemodynamic abn ormalities. Thus, anionic polysaccharides can inhibit SS RBC-endothelium in teraction in the presence or absence of soluble TSP. These agents may inter act with RBC membrane component(s) and prevent TSP-mediated adhesion of SS RBC to the endothelium, (C) 1999 by The American Society of Hematology.