In preclinical murine, rat, and canine ARDS/VILI studies, lung EC S1PR1 activation by intravenous-delivered S1P or S1P analogs rapidly initiates a signaling cascade that reorganizes the EC cytoskeleton, enhances junctional integrity, decreases alveolar edema formation, and markedly improves oxygenation (139). This evidence concerns the gene S1PR1 and acute respiratory distress syndrome.