Neutrophil-endothelial cell interactions in vivo: a chain of events characterized by distinct molecular mechanisms

Several sequential steps characterized by distinct molecular mechanisms are required for intravascular neutrophil adhesion in acute inflammation under the unique physical conditions found in the microvasculature in vivo. Adhesion is initiated by L-selectin, a constitutively functional glycoprotein on circulating neutrophils which may interact with several ligands on inflamed endothelial cells. L-selectin binding allows margination and rolling of neutrophils in venules. Subsequently, rolling cells may encounter activating or chemotactic stimuli which trigger functional upregulation of beta 2 integrins (CD11/CD18); the integrins mediate firm attachment and are required for diapedesis. This paper will discuss the physiologic importance of L-selectin-mediated rolling and activation-induced beta 2 integrin engagement for neutrophil function in vivo.