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Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior.
Blood 1999; 93(4):1422-9Blood

Abstract

The abnormal adherence of sickle red blood cells (SS RBC) to vascular endothelium may play an important role in vasoocclusion in sickle cell anemia. Thrombospondin (TSP), unusually large molecular weight forms of von Willebrand factor, and laminin are known to enhance adhesion of SS RBC. Also, these endothelial proteins bind to sulfated glycolipids and this binding is inhibited by anionic polysaccharides. Reversible sickling may expose normally cryptic 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, using cultured human umbilical vein endothelial cells (HUVEC) (for the adhesion assay) and the ex vivo mesocecum of the rat (for hemodynamic evaluation). The baseline adhesion (ie, without added TSP) of SS RBC to HUVEC was most effectively inhibited by high molecular weight dextran sulfate (HDS), whereas low molecular weight dextran sulfate (LDS) and the glycosaminoglycan chondroitin sulfate A (CSA) also had significant inhibitory effects. Heparin was mildly effective whereas other glycosaminoglycans (chondroitin sulfates B and C, heparan sulfate, and fucoidan) were ineffective. Similarly, HDS and CSA resulted in an improved hemodynamic behavior of SS RBC. Soluble TSP caused significant increases in SS RBC adhesion and in the peripheral resistance. Both HDS and CSA prevented TSP-enhanced adhesion and hemodynamic abnormalities. Thus, anionic polysaccharides can inhibit SS RBC-endothelium interaction in the presence or absence of soluble TSP. These agents may interact with RBC membrane component(s) and prevent TSP-mediated adhesion of SS RBC to the endothelium.

Authors+Show Affiliations

Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9949187

Citation

Barabino, G A., et al. "Anionic Polysaccharides Inhibit Adhesion of Sickle Erythrocytes to the Vascular Endothelium and Result in Improved Hemodynamic Behavior." Blood, vol. 93, no. 4, 1999, pp. 1422-9.
Barabino GA, Liu XD, Ewenstein BM, et al. Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior. Blood. 1999;93(4):1422-9.
Barabino, G. A., Liu, X. D., Ewenstein, B. M., & Kaul, D. K. (1999). Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior. Blood, 93(4), pp. 1422-9.
Barabino GA, et al. Anionic Polysaccharides Inhibit Adhesion of Sickle Erythrocytes to the Vascular Endothelium and Result in Improved Hemodynamic Behavior. Blood. 1999 Feb 15;93(4):1422-9. PubMed PMID: 9949187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior. AU - Barabino,G A, AU - Liu,X D, AU - Ewenstein,B M, AU - Kaul,D K, PY - 1999/2/9/pubmed PY - 1999/2/9/medline PY - 1999/2/9/entrez SP - 1422 EP - 9 JF - Blood JO - Blood VL - 93 IS - 4 N2 - The abnormal adherence of sickle red blood cells (SS RBC) to vascular endothelium may play an important role in vasoocclusion in sickle cell anemia. Thrombospondin (TSP), unusually large molecular weight forms of von Willebrand factor, and laminin are known to enhance adhesion of SS RBC. Also, these endothelial proteins bind to sulfated glycolipids and this binding is inhibited by anionic polysaccharides. Reversible sickling may expose normally cryptic 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, using cultured human umbilical vein endothelial cells (HUVEC) (for the adhesion assay) and the ex vivo mesocecum of the rat (for hemodynamic evaluation). The baseline adhesion (ie, without added TSP) of SS RBC to HUVEC was most effectively inhibited by high molecular weight dextran sulfate (HDS), whereas low molecular weight dextran sulfate (LDS) and the glycosaminoglycan chondroitin sulfate A (CSA) also had significant inhibitory effects. Heparin was mildly effective whereas other glycosaminoglycans (chondroitin sulfates B and C, heparan sulfate, and fucoidan) were ineffective. Similarly, HDS and CSA resulted in an improved hemodynamic behavior of SS RBC. Soluble TSP caused significant increases in SS RBC adhesion and in the peripheral resistance. Both HDS and CSA prevented TSP-enhanced adhesion and hemodynamic abnormalities. Thus, anionic polysaccharides can inhibit SS RBC-endothelium interaction in the presence or absence of soluble TSP. These agents may interact with RBC membrane component(s) and prevent TSP-mediated adhesion of SS RBC to the endothelium. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9949187/Anionic_polysaccharides_inhibit_adhesion_of_sickle_erythrocytes_to_the_vascular_endothelium_and_result_in_improved_hemodynamic_behavior_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9949187 DB - PRIME DP - Unbound Medicine ER -