Transendothelial migration induces rapid expression on neutrophils of granule-release VLA6 used for tissue...

Little is known of the mechanisms allowing neutrophils to infiltrate tissue after transendothelial migration. We postulated that VLA6 might be involved in neutrophil infiltration because it revealed as the most expressed beta1 integrins among VLA5, VLA4, and VLA3, which also appeared to define subsets within the blood neutrophil population. Transendothelial migration up-regulated by threefold (5,000 to 15,000 receptors) VLA6 expression on neutrophils. VLA6 up-regulation was transient, peaking in 6 min and returning to baseline in 1 h when tested in response to N-formyl-methionyl-leucyl-phenylalanine. Neutrophil degranulation experiments revealed a steady correlation between expression of VLA6 and granule content release, notably beta-glucuronidase, indicating that VLA6 molecules were preformed and stored mostly in azurophilic granules. Migration across fibroblast monolayers of neutrophils preactivated for VLA6 up-regulation was blocked when they were preincubated with anti-VLA6. However, anti-VLA6 had no effect on transfibroblast migration of non-preactivated neutrophils. These results indicate that VLA6 was functional only on activated neutrophils that used their up-regulated VLA6 to cross fibroblasts. Activation of neutrophils by transendothelial migration induces rapid expression of granule release VLA6 that appears to be a key adhesion mechanism used by a subset of neutrophils to infiltrate tissue.