The role of endothelial PI3Kactivity in neutrophil trafficking

摘要: Phosphoinositide 3-kinase gamma (PI3K) in neutrophils plays a critical role the directed migration of these cells into inflamed tissues. In this study, we demonstrate importance endothelial component PI3K activity relative to its leukocyte counterpart supporting neutrophil interactions with vessel wall. Despite reconstitution class-Ib function p110 / mice, observed 45% reduction accumulation an acute lung injury model. Mechanistically, appears result from perturbation selectin-mediated adhesion as manifested by 70% wild-type (WT) attachment and 17-fold increase rolling velocities on microvessels vivo response tumor necrosis factor alpha (TNF). This alteration was further augmented deficiency p110, suggesting that both catalytic subunits is required for efficient capture cytokinestimulated endothelium. Interestingly, Eselectin‐mediated mice impaired more than 95%, but no defect nuclear kappa B (NFB)‐induced gene expression observed. These findings suggest previously unrecognized partnership between class-I PI3Ks expressed leukocytes endothelium, combination which trafficking immunocompetent sites inflammation. (Blood. 2005;106:150-157)