Alternatively, S1P disrupts barrier integrity in the inflamed lung through sphingosine-1-phosphate receptor-3 (S1PR3), the receptor encoded by the ARDS candidate gene S1P3, which in contrast to S1PR1-mediated Rac1-signaling, exerts permeability in a RhoA-dependent manner. This evidence concerns the gene RAC1 and acute respiratory distress syndrome.