Regulatory pathways which govern neutrophil activation and extravasation. After tissue injury or pathogen invasion, cytokines produced by resident leukocytes or metabolites generated by pathogens induce endothelial cell activation. Activated endothelial cells mobilize P-selectin and E-selectin to the apical cell surface which facilitates loose neutrophil adhesion through interactions with PSGL-1. Activation of neutrophils during loose adhesion results in conformational changes in integrins that mediate firm adhesion and extravasation. Once extravasated, neutrophils respond to chemotactic stimuli, neutralize pathogens and remove necrotic tissue through the collaboration of a wide variety of factors, including enzymes and free radicals.