A co-stimulatory signal through ICAM-beta(2) integrin-binding potentiates neutrophil phagocytosis

The beta(2) integrin LFA-1 (lymphocyte function associated antigen; CD11a/C D18) is the common ligand for the intercellular adhesion molecules(1-4) (IC AMs). Integrins support cell function by providing co-stimulatory second si gnals that are a precondition for full cell activation first described for ICAM-1-binding to LFA-1 in lymphocytes(3,4). Integrins can also serve to ac tivate functions associated with distinct subunits of other integrins(5). I n addition to LFA-1, neutrophils express the beta(2) integrin Mac-1 (CD11b/ CD18; CR3) that apparently contains multiple sites that bind invading micro bes directly or through surface-fixed C3 (ref. 6), resulting in activation of the phagocyte function(7-11). Expression of the LFA-1 counter-receptor I CAM-1 on endothelial cells occurs only at the site of inflammation(12,13). Therefore, in neutrophils, ICAM-1 ligand binding could, as with lymphocytes , also play a part as a costimulatory signal to induce full phagocytotic fu nction. We show that in neutrophils, the LFA-1 ligand interaction is the st imulatory signal to express full phagocytotic activation. This is best demo nstrated by the rapid association of Streptococcus pyogenes with neutrophil s, followed by ingestion, strong oxidative-burst induction and enhanced kil ling of these bacteria, which are well-known for their resistance to human neutrophil defense. These findings may contribute to the development of the rapeutic strategies targeting the modulation of ICAM-1-leukocyte interactio n.