Sickle cell VOC. SS-RBCs and other inflammatory mediators induce the activation of the endothelium. The damaged and stimulated endothelium is poised to recruit leukocytes. E-selectin on the endothelium is crucial for generating a secondary wave of activating signals, which produces a polarized expression of activated αMβ2 integrin (Mac-1) at the leading edge of the crawling neutrophil, allowing the capture of circulating discoid and sickle-shaped erythrocytes. These events culminate in VOC in the postcapillary venules.