John Libbey Eurotext



Sickle cell disease and cellular adherence Volume 4, issue 3, Mai-Juin 1998


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The classical pathophysiological scheme of sickle cell disease involves deoxi-hemoglobin S polymerization and subsequent sickling of the red blood cells (RBC). However, the fact that polymerization occurs after a delay time, which, in physiological conditions, is longer than the RBC transit time through the microcirculation has often been overlooked. The hypothesis that in addition RBC adheres to the endothelium was proposed in the early 80s. The identification of the proteins involved in this phenomenon, both on RBCs and on endothelial cells, has given a new credit to this hypothesis. Adhesion is mostly a characteristics of young erythroid cells, immature reticulocytes, expressing pro-adhesive proteins such as the VLA-4 integrin (alpha4beta1) and the glycoprotein CD36. Older, less deformable, cells are trapped in a second step, contributing to a complete vascular plugging. Proteic partners at the endothelial cell surface are CD36, and, after activation by pro-inflammatory cytokines, the VCAM-1 receptor. The later binds VLA-4 directly whereas plasmatic thrombospondin serves as a bridge between the two CD36 molecules. Other low affinity interactions have been reported which are probably of functional relevance, most particularly that involving the von Willebrand factor (vWF). Actually, different mechanisms seem to prevail, depending upon the circumstances and the vascular bed. CD36 is present on the endothelial cells of the microvasculature ; VCAM-1 is expressed only on an activated endothelium ; the involvement of vWF seems restricted to large vessels. The clotting and hemostasis systems probably have an important participation to the overall phenomenon, as well as most of the other circulating cells. Even though many aspects still need to be better understood, these data provide a different light on the pathogenesis of vascular occlusion in sickle cell disease, outlining the role of concurrent illness. New biological and clinical fields of investigation are open, which may potentially lead to new therapeutic targets.