Visualizing S1P-directed cellular egress by intravital imaging

• S1P signals through S1P1 to stimulate cell egress into the circulation.
• Two-photon intravital microscopy visualizes dynamic processes in vivo in real time.
• Two-photon intravital microscopy has visualized S1P1-directed cellular egress.
• S1P1-dependent egress processes for different cell types share common features.

Sphingosine-1-phosphate (S1P) is a bioactive lipid that provides cellular signals through plasma membrane G protein-coupled receptors. The S1P receptor signaling system has a fundamental and widespread function in licensing the exit and release of hematopoietically derived cells from various tissues into the circulation. Although the outlines of the mechanism have been established through genetic and pharmacologic perturbations, the temporal and spatial dynamics of the cellular events involved have been unclear. Recently, two-photon intravital imaging has been applied to living tissues to visualize the cellular movements and interactions that occur during egress processes. Here we discuss how some of these recent findings provide a clearer picture regarding S1P receptor signaling in modulating cell egress into the circulation. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.