The discovery of E-selectin in 1987 (1) culminated a series of experiments investigating the molecular basis of endothelial activation and interactions with leukocytes during acute inflammation. This initiated an era in which several additional endothelial structures involved in leukocyte adhesion were identified, and their roles in inflammation were investigated. Exploiting these insights to develop diagnostic and therapeutic interventions for inflammatory and other diseases remains a promising area of clinical investigation.

Bevilacqua and Gimbrone (1) identified monoclonal antibodies that blocked polymorphonuclear neutrophil (PMN) adhesion to inflammatory cytokine-activated human umbilical vein endothelial cells (HUVECs) and used them to expression-clone a cell surface glycoprotein, designated endothelial-leukocyte adhesion molecule (ELAM)-1, which mediates initial PMN adhesion to inflamed endothelium. ELAM-1 possessed a then-unique, complex mosaic structure predicting, for the first time, that inflammation involved calcium-dependent interactions between endothelial cell (EC) surface lectins and carbohydrate-bearing “counter-receptors” on circulating leukocytes. At about the same time, investigators studying seemingly unrelated cell–cell interactions during inflammation – one involving megakaryocytes and platelets, the other involving leukocytes – discovered two additional lectin-like molecules with similar but distinct mosaic structures. Thus was the selectin gene family defined (2–4), consisting of E-selectin (endothelium, CD62E, previously known as ELAM)-1, P-selectin (platelet, CD62P, previously known as platelet activation-dependent granule-to-external-membrane protein [PADGEM] and granule membrane protein of 140 kDa [GMP-140]), and L-selectin (leukocyte, CD62L, previously known as MEL-14 and leukocyte adhesion molecule [LAM]-1).