The non-receptor kinase Syk is mainly expressed in the hematopoietic system and plays a role in the maintenance of vascular integrity. Here, we demonstrate a role of Syk for cutaneous wound healing and for neutrophil (PMN) infiltration into the wounded tissue using wildtype mice reconstituted with a Syk deficient hematopoietic system. To study the functional impact of Syk for b2 integrin (CD11/CD18)-mediated PMN infiltration in more detail, we analyzed neutrophil-like differentiated HL-60 (dHL-60) cells expressing a Syk mutant (EGFP-Syk Y323F) that lacks the binding site of the class IA phosphatidylinositol 3-kinases (PI3K). EGFP-Syk Y323F transfectants formed multiple and instable lamellipodia and showed a migration defect suggesting an involvement of Syk in PI3K signaling. The expression of EGFP-Syk Y323F or the downregulation of Syk using siRNA technique impaired the enrichment of the class IA PI3K p110[delta] at the leading edge of dHL-60 cells. Moreover, the inhibition of Syk by piceatannol compromised the activity of PI3K at the leading edge. These data imply a novel role of Syk via PI3K p110[delta] signaling for b2 integrin-mediated migration which is a prerequisite for efficient PMN recruitment in vivo. (Supported by DFG: Wa 1048/2-3)