Figure 3.

Inside-out signaling cascade in neutrophils induced by selectin–ligand binding. Selectin-binding to P-selectin glycoprotein ligand-1 (PSGL-1) on the neutrophil surface, elicits a specific intracellular signaling pathway resulting in affinity activation of lymphocyte-function-associated antigen-1 (LFA-1). Downstream of selectin-PSGL-1-ligation, several signaling molecules including kinases, adapter proteins, and GTPases are activated. The complex signaling machinery results in conformational changes of LFA-1 from a bent conformation with low ligand binding affinity to an extended conformation with intermediate ligand binding affinity. Extended LFA-1 is able to bind ICAM-1 on the endothelial surface, promoting the transition from neutrophil rolling to slow rolling.