RT Journal Article
SR Electronic
T1 Allosteric LFA-1 Inhibitors Modulate Natural Killer Cell Function
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 355
OP 362
DO 10.1124/mol.108.051169
VO 75
IS 2
A1 Weitz-Schmidt, Gabriele
A1 Chreng, Stéphanie
A1 Riek, Simone
YR 2009
UL http://molpharm.aspetjournals.org/content/75/2/355.abstract
AB 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