A head-to-tail view of L-selectin and its impact on neutrophil behaviour

L-selectin is a type I transmembrane cell adhesion molecule expressed on most circulating leukocytes, including neutrophils. Engagement of L-selectin with endothelial-derived ligands initiates neutrophil tethering and rolling behaviour along luminal walls of post-capillary venules, constituting the first step of the multi-step adhesion cascade. There is a large body of evidence to suggest that signalling downstream of L-selectin can influence neutrophil behaviour: adhesion, migration and priming. This review will cover aspects of L-selectin form and function and introduce the “triad of L-selectin regulation”, highlighting the inextricable links between adhesion, signalling and ectodomain shedding and also highlighting the cytosolic proteins that interconnect them. Recent advances in how L-selectin impacts priming, transendothelial migration (TEM) and cell polarity will also be discussed.