Natural killer cells adhere to bone marrow fibroblasts and inhibit adhesion of acute myeloid leukemia cells.

In this study we have demonstrated that natural killer (NK) cells adhere to elements of the bone marrow stroma (BMS) including fibroblasts, fibronectin and laminin but not to collagen type I, vitronectin and hyaluronic acid. NK cells bind to fibronectin and laminin using the beta 1 integrins VLA-4 and VLA-5, and VLA-6 respectively. The mechanism of adhesion to bone marrow fibroblasts is more complicated with beta 1 and beta 2 integrins being partially responsible but the majority of adhesion remaining unexplained. IL-2 stimulation of NK cells resulted in an increase in the expression of adhesion molecules involved in binding of NK cells to bone marrow fibroblasts (BMF) and extracellular matrix (ECM) proteins including the beta 1 chain CD29, alpha chains of VLA-4 and 5, beta 2 chain CD18 and alpha L chain CD11a. A marked increase in expression of beta 7 was also observed. There was a significant increase in the adhesion of NK cells to fibronectin in response to IL-2 treatment. NK cells also bound more strongly to BMF following IL-2 treatment although the development of cytotoxicity appeared to interfere with the adhesion assay. NK cells competitively inhibit the binding of AML blasts but not ALL blasts to BMF. Mechanisms underlying the inhibition of leukemic growth by NK and LAK cells may include direct and cytokine mediated cytotoxicity and perturbation of the interaction of leukemic blasts with the bone marrow stroma which is essential for blast cell survival.