Interaction of natural killer cells with extracellular matrix induces early intracellular signalling events and enhances cytotoxic functions

NK cells are endowed with a wide array of adhesion molecules which mediate their interaction with endothelium and extracellular matrix components. We have shown that cross-linking of β1 integrins and CD44 on human NK cells induces a signal transduction pathway involving both tyrosine kinase activation and the modulation of intracellular calcium levels. Our studies have also demonstrated the ability of β1 integrins and CD44 to upregulate both the spontaneous and the CD16-triggered cytotoxic activity of human NK cells. Although the molecular mechanisms responsible for this costimulatory activity have not been defined yet, our studies indicate that the simultaneous cross-linking of β1 integrins and CD44 results in a synergistic effect on CD16-mediated enhancement of intracellular free calcium concentration, and suggest that this may be relevant for the cooperation observed.