Sphingolipids and lung vascular barrier regulation

Long thought to function primarily as the structural components of lipid membranes, sphingolipids are now also recognized as vitally important signaling mediators regulating a diverse range of functions. We recently described the potent vascular barrier-regulating properties of one of these sphingolipids, the lipid and angiogenic factor sphingosine 1-phosphate (S1P) (Garcia et al, 2001). Since disruption of vascular barrier integrity commonly occurs in highly morbid inflammatory lung conditions, a better understanding of the mechanism of barrier regulation would have important clinical implications. In this chapter, we provide a brief overview of vascular barrier regulation before detailing the mechanisms underlying potent barrier-enhancing effects of S1P in vitro and in vivo in models of acute lung injury (ALI) syndromes. The potential ramifications of these findings for the development of specific therapeutic interventions for patients with ALI syndromes are then discussed.