Lymphocyte function-associated antigen-1 blockade by statins: molecular basis and biological relevance

Abstract

Lymphocyte function-associated antigen-1 (LFA-1) belongs to the integrin family and plays an important role in leukocyte trafficking and in T-cell activation. Random screening of chemical libraries identified the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin as an inhibitor of the LFA-1/intercellular adhesion molecule (ICAM)-1 interaction. The effect of lovastatin on LFA-1 was found to be unrelated to the inhibition of HMG-CoA reductase and to be mediated by lovastatin binding to a novel allosteric site within LFA-1. The biological relevance of LFA-1 inhibition by statins with respect to the overall benefit of this drug class is reviewed. The implications of the statin effect on LFA-1 for future drug design and therapy are discussed.