TY - JOUR T1 - Allosteric LFA-1 Inhibitors Modulate Natural Killer Cell Function JF - Molecular Pharmacology JO - Mol Pharmacol SP - 355 LP - 362 DO - 10.1124/mol.108.051169 VL - 75 IS - 2 AU - Gabriele Weitz-Schmidt AU - Stéphanie Chreng AU - Simone Riek Y1 - 2009/02/01 UR - http://molpharm.aspetjournals.org/content/75/2/355.abstract N2 - Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant rejection and autoimmunity. None of the therapeutic modalities currently available are known to potently interfere with NK cell activity. Here we demonstrate for the first time that low molecular weight inhibitors of the integrin lymphocyte function-associated antigen-1 (LFA-1) readily block NK cell adhesion, activation, and NK cell-mediated cytolysis in vitro, in contrast to other immunosuppressive agents. These effects were independent of the type of allosteric mechanism by which LFA-1 inhibition was achieved. In addition, we describe a simple, nonradioactive whole-blood assay that should be suitable to monitor NK cell activation in clinical practice. Taken together, our study underlines the importance of LFA-1 in NK cell effector functions and indicates that allosteric LFA-1 inhibitors may become important tools to further elucidate the therapeutic potential of NK cell modulation in immunological diseases. The American Society for Pharmacology and Experimental Therapeutics ER -