Early in the inflammatory response, neutrophils infiltrate tissues by migrating (extravasating) across the endothelium of blood vessels, then moving chemotactically towards the site of inflammation. The expression of the cell-surface adhesion protein JAM-A in endothelial cells is thought to affect neutrophil extravasation – but does JAM-A expressed in neutrophils also function in infiltration? On , Elisabetta Dejana and colleagues show that it does. The authors have previously demonstrated that, in vitro, JAM-A expression in neutrophils is needed for their efficient directional migration; now, they show that the migration of leukocytes after extravasation is impaired in JAM-A-deficient mice. In activated HL60 neutrophils, they show, JAM-A is internalised into intracellular vesicles that also contain several integrins. Moreover, cell-surface JAM-A co-clusters with β1 integrin in the presence of fibronectin-coated beads or anti-integrin antibodies. Importantly, the internalisation of integrins by neutrophils derived from JAM-A-deficient mice in response to chemotactic signals is impaired, affecting both uropod retraction and cell motility. On the basis of these and other data, the authors propose that JAM-A promotes neutrophil chemotaxis by controlling integrin internalisation and recycling.
