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 beta-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 beta-1, alpha-3, alpha-4, and alpha-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 beta-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 alpha-4 or alpha-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.
Department of Experimental Medicine, University of Roma, Italy.
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Gismondi
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Morrone
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Humphries
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Piccoli
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Frati
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Santoni
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001665:Binding Sites; D019002:CD56 Antigen; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011961:Receptors, Fc / Q000032:analysis; D017469:Receptors, Fibronectin; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000378:metabolism*; D016029:Receptors, Very Late Antigen / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D005353:Fibronectins; D011961:Receptors, Fc; D017469:Receptors, Fibronectin; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D016029:Receptors, Very Late Antigen