Cell adhesion molecules: selectins and integrins.

Cell adhesion molecules play a key role in different physiological and pathological phenomena. Selectins comprise a family of three members (E-, P-, and L-selectin) that are differentially expressed by leukocytes and endothelial cells, and are involved in the early steps of leukocyte extravasation. Although many different putative ligands of selectins have been described, their physiological relevance has not been elucidated in all cases. Selectins and some of their counter-receptors function also as signal-transducing receptors, significantly contributing to leukocyte and endothelial cell activation. Integrins represent a large family of adhesion receptors that are widely expressed and mainly interact with extracellular matrix components. The affinity and avidity of integrins can be modulated by different mechanisms triggered either from the extracellular milieu or through intracellular signals. Integrins show a close relationship with cytoskeleton and exert an important role as signal-transducing receptors, activating different biochemical pathways, mainly the mitogen-activated protein (MAP) kinase cascade. In addition to their adhesive function, these receptors modulate key intracellular phenomena, including cell activation, proliferation, and apoptosis. Because selectins and integrins are involved in leukocyte extravasation and the inflammatory response, different strategies are in progress for the blockade of these molecules and, therefore, for therapy of inflammatory diseases.