Role of mononuclear cells in the pathophysiology of SCD. Vaso-occlusion and tissue injury lead to activation of the mononuclear cells and the release of proinflammatory cytokines. This leads to further adhesion of sickle red cells and leukocytes to the vascular endothelium perpetuating the vicious cycle of vaso-occlusion and inflammation. CAM, cell adhesion molecule; EC, endothelial cell; MN, monocyte; PLGF, placental growth factor; PMN, polymorphonuclear leukocyte; SRBC, sickle red blood cell; TSP/vWF, thrombospondin/von Willebrand factor. Professional illustration by Patrick Lane, ScEYEnce Studios.