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. 1992 Nov 1;176(5):1251–1257. doi: 10.1084/jem.176.5.1251

Triggering through CD16 or phorbol esters enhances adhesion of NK cells to laminin via very late antigen 6

PMCID: PMC2119439  PMID: 1402670

Abstract

Very late antigens VLA-1, VLA-2, VLA-3, and VLA-6, belonging to the beta 1 subfamily of integrins, have been identified as receptors for different binding domains of laminin (LM). We have detected VLA-6, but not VLA-1 and VLA-2 on a subset (50-70%) of fresh peripheral blood CD3- , CD16+, CD56+ human natural killer (NK) cells by immunofluorimetric and biochemical analysis. Binding assays performed on LM-coated plates showed that 10-15% of NK cells spontaneously adhere to LM, and this adhesion is mediated by VLA-6. Activation of NK cells through CD16 triggering or by phorbol ester results in a rapid increase of adhesion to LM, which is still mediated by VLA-6. The enhanced adhesiveness is not associated with changes in beta 1 LM receptor expression, while it correlates with changes in the phosphorylation status of alpha 6 subunit. The expression of VLA-6 on NK cells and the modulation of its avidity by activating stimuli may be relevant for NK cell migration and tissue location during inflammation or immune response.

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Selected References

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  1. Anegón I., Cuturi M. C., Trinchieri G., Perussia B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med. 1988 Feb 1;167(2):452–472. doi: 10.1084/jem.167.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bartolazzi A., Fraioli R., Tarone G., Natali P. G. Generation and characterization of the murine monoclonal antibody M-KID 2 to VLA-3 integrin. Hybridoma. 1991 Dec;10(6):707–720. doi: 10.1089/hyb.1991.10.707. [DOI] [PubMed] [Google Scholar]
  3. Buyon J. P., Slade S. G., Reibman J., Abramson S. B., Philips M. R., Weissmann G., Winchester R. Constitutive and induced phosphorylation of the alpha- and beta-chains of the CD11/CD18 leukocyte integrin family. Relationship to adhesion-dependent functions. J Immunol. 1990 Jan 1;144(1):191–197. [PubMed] [Google Scholar]
  4. Carman P. S., Ernst P. B., Rosenthal K. L., Clark D. A., Befus A. D., Bienenstock J. Intraepithelial leukocytes contain a unique subpopulation of NK-like cytotoxic cells active in the defense of gut epithelium to enteric murine coronavirus. J Immunol. 1986 Mar 1;136(5):1548–1553. [PubMed] [Google Scholar]
  5. Cassatella M. A., Anegón I., Cuturi M. C., Griskey P., Trinchieri G., Perussia B. Fc gamma R(CD16) interaction with ligand induces Ca2+ mobilization and phosphoinositide turnover in human natural killer cells. Role of Ca2+ in Fc gamma R(CD16)-induced transcription and expression of lymphokine genes. J Exp Med. 1989 Feb 1;169(2):549–567. doi: 10.1084/jem.169.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Conforti G., Zanetti A., Colella S., Abbadini M., Marchisio P. C., Pytela R., Giancotti F., Tarone G., Languino L. R., Dejana E. Interaction of fibronectin with cultured human endothelial cells: characterization of the specific receptor. Blood. 1989 May 1;73(6):1576–1585. [PubMed] [Google Scholar]
  7. Conforti G., Zanetti A., Pasquali-Ronchetti I., Quaglino D., Jr, Neyroz P., Dejana E. Modulation of vitronectin receptor binding by membrane lipid composition. J Biol Chem. 1990 Mar 5;265(7):4011–4019. [PubMed] [Google Scholar]
  8. Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
  9. Falcioni R., Sacchi A., Resau J., Kennel S. J. Monoclonal antibody to human carcinoma-associated protein complex: quantitation in normal and tumor tissue. Cancer Res. 1988 Feb 15;48(4):816–821. [PubMed] [Google Scholar]
  10. Gismondi A., Morrone S., Humphries M. J., Piccoli M., Frati L., Santoni A. Human natural killer cells express VLA-4 and VLA-5, which mediate their adhesion to fibronectin. J Immunol. 1991 Jan 1;146(1):384–392. [PubMed] [Google Scholar]
  11. Hemler M. E., Crouse C., Sonnenberg A. Association of the VLA alpha 6 subunit with a novel protein. A possible alternative to the common VLA beta 1 subunit on certain cell lines. J Biol Chem. 1989 Apr 15;264(11):6529–6535. [PubMed] [Google Scholar]
  12. Hemler M. E., Crouse C., Takada Y., Sonnenberg A. Multiple very late antigen (VLA) heterodimers on platelets. Evidence for distinct VLA-2, VLA-5 (fibronectin receptor), and VLA-6 structures. J Biol Chem. 1988 Jun 5;263(16):7660–7665. [PubMed] [Google Scholar]
  13. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  14. Hermanowski-Vosatka A., Van Strijp J. A., Swiggard W. J., Wright S. D. Integrin modulating factor-1: a lipid that alters the function of leukocyte integrins. Cell. 1992 Jan 24;68(2):341–352. doi: 10.1016/0092-8674(92)90475-r. [DOI] [PubMed] [Google Scholar]
  15. Hibbs M. L., Jakes S., Stacker S. A., Wallace R. W., Springer T. A. The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site. J Exp Med. 1991 Nov 1;174(5):1227–1238. doi: 10.1084/jem.174.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hirst R., Horwitz A., Buck C., Rohrschneider L. Phosphorylation of the fibronectin receptor complex in cells transformed by oncogenes that encode tyrosine kinases. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6470–6474. doi: 10.1073/pnas.83.17.6470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  18. Marcantonio E. E., Guan J. L., Trevithick J. E., Hynes R. O. Mapping of the functional determinants of the integrin beta 1 cytoplasmic domain by site-directed mutagenesis. Cell Regul. 1990 Jul;1(8):597–604. doi: 10.1091/mbc.1.8.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morrone S., Scarpa S., Punturieri A., Testi R., Gismondi A., Santoni G., Piccoli M., Frati L., Modesti A., Santoni A. Laminin synthesis by NK cells and modulation of its expression by TPA (12-O-tetradecanoylphorbol-13-acetate). Exp Cell Res. 1989 Jun;182(2):543–549. doi: 10.1016/0014-4827(89)90257-7. [DOI] [PubMed] [Google Scholar]
  20. O'Shea J. J., Weissman A. M., Kennedy I. C., Ortaldo J. R. Engagement of the natural killer cell IgG Fc receptor results in tyrosine phosphorylation of the zeta chain. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):350–354. doi: 10.1073/pnas.88.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. O'Toole T. E., Mandelman D., Forsyth J., Shattil S. J., Plow E. F., Ginsberg M. H. Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb. Science. 1991 Nov 8;254(5033):845–847. doi: 10.1126/science.1948065. [DOI] [PubMed] [Google Scholar]
  22. Perussia B., Trinchieri G., Jackson A., Warner N. L., Faust J., Rumpold H., Kraft D., Lanier L. L. The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. J Immunol. 1984 Jul;133(1):180–189. [PubMed] [Google Scholar]
  23. Prichard M. G., Boerth L. W., Pennington J. E. Compartmental analysis of resting and activated pulmonary natural killer cells. Exp Lung Res. 1987;12(3):239–251. doi: 10.3109/01902148709064303. [DOI] [PubMed] [Google Scholar]
  24. Schwarz R. E., Hiserodt J. C. The expression and functional involvement of laminin-like molecules in non-MHC restricted cytotoxicity by human Leu-19+/CD3- natural killer lymphocytes. J Immunol. 1988 Nov 15;141(10):3318–3323. [PubMed] [Google Scholar]
  25. Shaw L. M., Messier J. M., Mercurio A. M. The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin. J Cell Biol. 1990 Jun;110(6):2167–2174. doi: 10.1083/jcb.110.6.2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shimizu Y., Van Seventer G. A., Horgan K. J., Shaw S. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature. 1990 May 17;345(6272):250–253. doi: 10.1038/345250a0. [DOI] [PubMed] [Google Scholar]
  27. Timpl R. Structure and biological activity of basement membrane proteins. Eur J Biochem. 1989 Apr 1;180(3):487–502. doi: 10.1111/j.1432-1033.1989.tb14673.x. [DOI] [PubMed] [Google Scholar]
  28. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376. doi: 10.1016/S0065-2776(08)60664-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wiltrout R. H., Mathieson B. J., Talmadge J. E., Reynolds C. W., Zhang S. R., Herberman R. B., Ortaldo J. R. Augmentation of organ-associated natural killer activity by biological response modifiers. Isolation and characterization of large granular lymphocytes from the liver. J Exp Med. 1984 Nov 1;160(5):1431–1449. doi: 10.1084/jem.160.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]

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