Roles of phospholipid signaling in chemoattractant-induced responses.

Chemoattractants, including chemokines, play a central role in regulation of inflammatory reactions by attracting and activating leukocytes. These molecules have been found to regulate metabolism of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) via phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K). Recent studies of mouse lines that lack PLC-(beta)2, PLC-(beta)3, or PI3K(gamma) demonstrate that chemoattractants act through PLC-(beta)2 and PLC-(beta)3 to hydrolyze PtdIns(4,5)P(2) and through PI3K(gamma) to phosphorylate PtdIns(4,5)P(2) in mouse neutrophils. These studies also confirmed the importance and revealed new roles of these signaling pathways in chemoattractant-induced responses.