Sickle cell vasoocclusion: heterotypic, multicellular aggregations driven by leukocyte adhesion.

Homozygous expression of sickle beta-globin alters the function of blood cells and the endothelium, producing a wide spectrum of clinical manifestations. Intravital microscopy studies in sickle cell mice suggest that vasoocclusion is a complex, sequential, multistep phenomenon involving (1) endothelial activation by sickle erythrocyte (SSRBC), (2) leukocyte (WBC) adhesion to the endothelium, and (3) the direct interaction between SSRBCs and adherent WBCs, which leads to reduced blood flow and tissue ischemia. Each of these steps represents a potentially useful therapeutic target. The identification of molecular determinants mediating vasoocclusion will provide new strategies for the prevention and treatment of this debilitating illness.