Functional analysis of α1β1 integrin in human natural killer cells

Juan J. Pérez-Villar, Ignacio Melero, Angela Gismondi, Angela Santoni, Miguel López-Botet

Research output: Contribution to journalArticle

Abstract

Upon activation with interleukin (IL)-2 human natural killer (NK) cells acquire on their surface the α1β1 and α2β1 integrins and down-regulate the expression of α6β1. By employing α1β1-specific monoclonal antibody (mAb) HP-2B6, characterized in our laboratory, we examined the functional role of the α1β1 integrin in NK cells. Treatment with HP-2B6 mAb partially interfered with attachment of cultured NK cells to type I collagen, and combined with an anli-α2β1 (TEA 1/41) mAb, it completely abrogated cell adhesion to this extracelular matrix protein. In contrast, NK cell attachment to laminin was completely blocked by the anti-β1 LIA 1/2 mAb, but was unaffected by α1 and α2-specific mAb; as α3β1 and α6β1 were undetectable, the data indicate that the α1β1 integrin binding sites for type I collagen and laminin are different. Incubation with anti-α1 HP-2B6 or its F(ab')2 fragments specifically induced a rapid homotypic aggregation of NK cells that was dependent on active metabolism, an intact cytoskeleton and the presence of divalent cations (Ca2+ and Mg2+); homotypic cell adhesion was selectively blocked by anti-CD18, CD11a or CD54 mAb. In addition, stimulation of cultured NK cells with the anti-α1 HP-2B6 enhanced TNF-α production and induced tyrosine phosphorylation of a 110-kDa protein. Pretreatment with specific inhibitors of protein tyrosine kinase (PTK) activity (tyrphostin 25 and herbimycin A) completely abrogated the functional effects induced by the anti-α1 HP-2B6 mAb. Our data show that ligation of the α1β1 integrin positively modulates IL-2-activated NK cell function via a PTK-dependent pathway.

Original languageEnglish
Pages (from-to)2023-2029
Number of pages7
JournalEuropean Journal of Immunology
Volume26
Issue number9
Publication statusPublished - 1996

Keywords

  • Extracellular matrix protein
  • Integrin
  • Natural killer
  • Tumor necrosis factor-α
  • Very late antigen-1

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Pérez-Villar, J. J., Melero, I., Gismondi, A., Santoni, A., & López-Botet, M. (1996). Functional analysis of α1β1 integrin in human natural killer cells. European Journal of Immunology, 26(9), 2023-2029.