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 beta 1 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 beta 1 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 beta 1 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.
Palmieri
G
G
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Gismondi
A
A
Galandrini
R
R
Milella
M
M
Serra
A
A
De Maria
R
R
Santoni
A
A
D002450:Cell Communication / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005109:Extracellular Matrix / Q000276:immunology*; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*