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

Very late antigens VLA-1, VLA 2, VLA-3, and VLA6, belonging to the 01 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 (31 LM receptor expression, while it correlates with changes in the phosphorylation status of cx6 subunit . The expression of VLA6 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. N K cells are a heterogenous population of CD3 -, CD16`, CD56+ large granular lymphocytes (LGL)' capable of lysing a broad range of neoplastic, normal, and virus-infected cells in a non-MHC-restricted or antibodydependent manner (antibody-dependent cell-mediated cytotoxicity [ADCC]) (1) . CD16 is a low affinity receptor for the Fc fragment of IgG (Fc-yRIII) (2) and represents one of the most important signal transduction structures capable of activating the NK cell functional program (1) . NK cells mainly circulate in the peripheral blood, and also can be found under physiologic and inflammatory conditions in several nonlymphoid tissues, including lung interstitium (3), intestinal mucosa (4), and liver (5) . This recirculation pattern indicates that they interact with endothelial cells, as well as with several extracellular matrix (ECM) components .