beta(1) integrin activation on human neutrophils promotes beta(2) integrin-mediated adhesion to fibronectin

Although the importance of beta (1) integrin-mediated binding to adhesion m olecules and extracellular matrix (ECM) molecules is well established for m ost types of leukocytes, the expression patterns and functional importance of B-1 integrins on neutrophils have remained controversial. Using flow cyt ometry, we found that human neutrophils express the alpha (4), alpha (5), a lpha (9) and beta (1) integrin subunits. To examine whether the integrins V LA-4 (alpha (4)/beta (1)) and VLA-5 (alpha (5)/beta (1),) have a functional role on neutrophils, we studied adhesion to their ligand fibronectin. Trea tment of neutrophils with antibody 8A2, which specifically binds and activa tes beta (1), integrins, resulted in increased binding to fibronectin. Howe ver, addition of blocking mAb revealed that 8A2-induced adhesion did not de pend on beta (1) integrins, but on the beta (2) integrin CD11b/CD18. Simila rly, activation of beta (1) integrins by 8A2 resulted in CD11b-dependent bi nding of neutrophils to fibrinogen. 8A2 treatment increased expression of a n activation epitope of CD11b/CD18, which depended on phosphoinositide 3-OH kinase activity and an adequate concentration of intracellular free Ca2+. These data suggest that engagement of beta (1) integrins on neutrophils res ults in a cross-talk signal that leads to activation of the beta (2) integr in CD11b/CD18, followed by CD11b-mediated adhesion. As transmigrated neutro phils are surrounded by both beta (1) and B-2 ligands in the ECM, this inte grin cross-talk could play a role in modifying migration and cellular activ ation in inflamed tissues.