Evidence for the involvement of phosphatidylinositol 3-kinase in fMLP-stimulated neutrophil adhesion to ICAM-1-transfected cells

Phosphatidylinositol 3-kinase (PI-3K) controls important intracellular step s involved in inflammation, immunity, and cell growth. PI-3K also modulates leukocyte integrin adhesiveness. In this study we evaluated the role of PI -3K on neutrophil adhesion to intercellular adhesion molecule-1 (ICAM-1)-tr ansfected cells. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated neutrophil adhesion was inhibited by wortmannin and LY294002, two unrelated PI-3K inhibitors, whereas phorbol myristate acetate (PMA)-induced neutroph il adhesion was not inhibited by them. After fMLP stimulation, a rapid acti vation of AKT and ERK was observed. However, only activation of AKT was rev ersed by the PI-3K inhibitors. Neutrophil expression of the beta (2)-integr ins Mac-1, lymphocyte function-associated antigen-1(LFA-1), and gp150.95 wa s not affected by wortmannin, nor was expression of the activation epitope recognized by MAB24. We conclude that (a) PI-3K is involved in fMLP-activat ed neutrophil adhesion to ICAM-1-transfected cells, (b) the mechanism invol ved is not mediated by the modulation of beta (2)-integrin expression or ac tivation, and (c) another mechanism seems to involve the adhesion to ICAM-1 when a cellular system of adhesion is used.