Human natural killer cells express VLA-4 and VLA-5, which mediate their adhesion to fibronectin

Very late Ag (VLA)-3, VLA-4, and VLA-5, belonging to the β-1 subfamily of integrins, have been recently identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3, on fresh CD3^-, CD16⁺, CD56⁺ human NK cells by flow cytometry and immunochemical analyses using mAb directed against β-1, α-3, α-4, and α-5 subunits. Binding assays, performed on FN-coated plates, showed that NK cells specifically adhere to FN and their binding capacity is increased by MgCl₂ but not by CaCl₂. Using as inhibitory probes a polyclonal antibody against the β-1 chain of the human FN receptor, the synthetic peptide GRGDSP, which is able to inhibit cellular adhesion mediated by VLA-5, the CS1 fragment, which contains the principal adhesion site in the IIICS domain recognized by VLA-4, and functional mAb directed against α-4 or α-5 subunits, we show that both VLA-4 and VLA-5 mediate the adhesion of human NK cells to FN. The expression of these integrin receptors may be relevant for NK interaction with extracellular matrix components and other cell types.