Lysophospholipids as mediators of immunity

Lysophospholipids (LPLs) are lipid-derived signaling molecules exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Originally identified as serum-associated growth factors, these mediators now are known to signal through a family of diverse G protein-coupled receptors (GPCRs). Virtually all cells that participate in the immune response express multiple receptors for LPLs. The development of antibody reagents that recognize the receptors for each LPL and the derivation of receptor-selective agonists and receptor-null mouse strains have provided insights into the widely diverse functions of LPLs in immune responses, particularly the role of S1P in lymphocyte trafficking. This review focuses on the biology of the LPLs as these molecules relate to functional regulation of immune cells in vitro and to the regulation of integrated immune responses in vivo.