title: Molecular basis of sickle cell-endothelial cell interactions.
abstract: Adherence of sickle erythrocytes to microvascular endothelium is posited to initiate or contribute to sickle cell vaso-occlusive pain episodes. Adherence and occlusion in vivo may depend on hemodynamics interacting with plasma, erythrocyte, and endothelial cell factors. Four receptor-mediated adherence pathways have been described to date: adherence mediated by high molecular weight von Willebrand factor multimers bridging glycoprotein lb-like and integrin receptors on sickle cells and similar receptors on endothelial cells; thrombospondin bridging CD36 on sickle reticulocytes and the alpha v beta 3 integrin on large-vessel endothelial cells or alpha v beta 3 and CD36 on microvascular endothelium; binding of sickle reticulocyte alpha 4 beta 1 receptors to vascular cell adhesion molecule 1 expressed on endothelial cells stimulated by cytokine or double-stranded RNA viruses; and binding of sickle cells to endothelial cell-associated fibronectin via sickle reticulocyte alpha 4 beta 1 activated by phorbol ester or interleukin-8. The significance of these adherence pathways in sickle cell vaso-occlusion is discussed.
authors.affiliation: School of Chemical Engineering, Georgia Institute of Technology, Atlanta 30332-0100, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Wick
authors.forename: J R
authors.initials: JR
authors.lastname: Eckman
mesh_terms: D004730:Endothelium, Vascular / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D006450:Hemoglobin SC Disease / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013314:Stress, Mechanical; D019699:Thrombospondins / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology; D014841:von Willebrand Factor / Q000502:physiology
chemical_list: D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019699:Thrombospondins; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor