Lysophosphatidic Acid

Abstract

Among the various phospholipid derived signaling molecules, relatively little attention has been paid to lysophospholipids as potential messengers. This is perhaps not too surprising in view of the detergentlike and lytic properties of many of these lipids. However, one notable exception is lysophosphatidic acid (LPA) or monoacyl-glycerol-3-phosphate, the smallest and structurally simplest of all (lyso)phospholipids. LPA evokes striking hormone- and growth factor-like effects when added exogenously to intact cells at submicromolar doses, far below the critical micelle concentration (Moolenaar, 1994; Jalink et al., 1994a). LPA is rapidly produced and released by activated platelets and, as such, is a normal constituent of serum (but not plasma), where it is present in an albumin-bound form (Eichholtz et al.,1993). Although its precise physiological and pathological functions in vivo remain to be explored, platelet-derived LPA has all the hallmarks of an important growth factor that may participate in wound healing and tissue remodeling. Thus, LPA not only stimulates the growth of fibroblasts (van Corven et al.,1989; Tigyi et al., 1994), vascular smooth muscle cells (Tokumura et al., 1994), and keratinocytes (Piazza et al.,1995), it also promotes cellular tension (Kolodney and Elson, 1993) and cell-surface fibronectin binding (Zhang et al., 1994), which are important events in wound repair. Where tested, cellular responses to LPA show a striking overlap with those to whole serum; it therefore seems safe to conclude that LPA (albumin-bound) accounts for much of the biological activity of serum.