Model for E-selectin–mediated slow rolling. The circled numbers represent new signaling components identified in this paper. Neutrophils rolling on E-selectin engage both CD44 and PSGL-1 to initiate signaling through a common pathway that requires lipid rafts, the cytoplasmic domain of PSGL-1, all 3 SFKs, the ITAM adaptors DAP12 and FcRγ, the Tec kinase Btk, and p38. This signaling cascade activates integrin leukocyte function-associated antigen 1 (LFA-1) to a conformation that enables slow rolling but not arrest on ICAM-1. PSGL-1 and CD44 may not be located in the same raft domains as depicted in the figure.