Cross-linking of α4β1 and α5β1 fibronectin receptors enhances natural killer cell cytotoxic activity

G. Palmieri, A. Serra, R. De Maria, A. Gismondi, M. Milella, M. Piccoli, L. Frati, A. Santoni

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Cell/extracellular matrix interactions mediated by integrins regulate differentiation, migration, and effector functions of immune system components. Human NK cells express α4β1 and α5β1 integrins, which mediate their binding to fibronectin (FN). We have investigated the ability of FN and its β1 integrin receptors to modulate NK cytotoxicity. Our data show that the presence of immobilized FN significantly augments the spontaneous cytotoxic activity of in vitro cultured human NK cells against several NK- susceptible, but not NK-resistant, target cells; Ab-dependent cytotoxicity against Ab-coated P815 target cells and the redirected lysis of anti-CD16 hybridomas are also enhanced in the presence of FN. Solid-phase-bound anti- human β1, or its F(ab')2 fragment, anti-α4 and anti-α5 mAbs, all consistently enhance Ab-dependent cytotoxicity against Ab-coated murine target cells. The 120-kDa (α5β1-binding), but not the 40-kDa (α4β1- binding), FN fragment fully reproduced the enhancing effect observed with the entire molecule. Our data also demonstrate that α4β1 and α5β1 cross- linking on NK cells induces an increase of intracellular Ca2+ concentration that is abrogated by EGTA, thus suggesting that the capacity to mobilize Ca2+ is involved in the coactivating role of α4β1 and α5β1 FN receptors in the cytotoxic functions of NK cells.

Original languageEnglish
Pages (from-to)5314-5322
Number of pages9
JournalJournal of Immunology
Issue number11
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology


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