TRANSENDOTHELIAL MIGRATION INDUCES RAPID EXPRESSION ON NEUTROPHILS OFGRANULE-RELEASE VLA6 USED FOR TISSUE INFILTRATION

Little is known of the mechanisms allowing neutrophils to infiltrate t issue after transendothelial migration. We postulated that VLA6 might be involved in neutrophil infiltration because it revealed as the most expressed beta(1) integrins among VLA5, VLA4, and VLA3, which also ap peared to define subsets within the blood neutrophil population. Trans endothelial migration up-regulated by threefold (5,000 to 15,000 recep tors) VLA6 expression on neutrophils. VLA6 up-regulation was transient , peaking in 6 min and returning to baseline in 1 h when tested in res ponse to N-formyl-methionyl-leucyl-phenylalanine. Neutrophil degranula tion experiments revealed a steady correlation between expression of V LA6 and granule content release, notably beta-glucuronidase, indicatin g that VLA6 molecules were preformed and stored mostly in azurophilic granules. Migration across fibroblast monolayers of neutrophils preact ivated for VLA6 up-regulation was blocked when they were preincubated with anti-VLA6. However, anti-VLA6 had no effect on transfibroblast mi gration of non-preactivated neutrophils. These results indicate that V LA6 was functional only on activated neutrophils that used their up-re gulated VLA6 to cross fibroblasts. Activation of neutrophils by transe ndothelial migration induces rapid expression of granule release VLA6 that appears to be a key adhesion mechanism used by a subset of neutro phils to infiltrate tissue.