The study by Muller et al. investigates the role of platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) in the transendothelial migration of leukocytes. They find that anti-PECAM antibodies or recombinant soluble PECAM significantly block the transendothelial migration of monocytes and neutrophils, while not affecting chemotaxis. Light and electron microscopy reveal that blocked leukocytes remain tightly bound to the apical surface of the endothelial cells, specifically over the intercellular junctions. The process of leukocyte emigration is divided into three stages: rolling mediated by selectins, tight adhesion mediated by integrins, and transmigration, which requires PECAM-1. The study demonstrates that PECAM-1 plays a crucial role in the transendothelial migration of both monocytes and neutrophils, and suggests potential therapeutic targets for inflammatory diseases.The study by Muller et al. investigates the role of platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) in the transendothelial migration of leukocytes. They find that anti-PECAM antibodies or recombinant soluble PECAM significantly block the transendothelial migration of monocytes and neutrophils, while not affecting chemotaxis. Light and electron microscopy reveal that blocked leukocytes remain tightly bound to the apical surface of the endothelial cells, specifically over the intercellular junctions. The process of leukocyte emigration is divided into three stages: rolling mediated by selectins, tight adhesion mediated by integrins, and transmigration, which requires PECAM-1. The study demonstrates that PECAM-1 plays a crucial role in the transendothelial migration of both monocytes and neutrophils, and suggests potential therapeutic targets for inflammatory diseases.