Lysophosphatidic acid enhances healing of acute cutaneous wounds in the mouse

Lysophosphatidic acid is a phospholipid growth factor and intercellular sig naling molecule released by activated platelets and injured fibroblasts tha t affects keratinocytes, fibroblasts, neutrophils,and monocytes. We therefo re hypothesized that lysophosphatidic acid could influence the inflammation and reepithelialization phases of wound healing. Lysophosphatidic acid (10 0 muM) was applied daily for 5 days to 2 mm-diameter excisional mouse ear s kin wounds and re-epithelialization was measured. We also evaluated whether the bioactivity of lysophosphatidic acid could be increased by zinc (Zn2+, 1 mM). Inflammatory cells were counted in wound sections after 1.3, or 5 d ays of healing. Reepithelialization was accelerated significantly by either lysophosphatidic acid or lysophosphatidic acid + Zn2- (p < 0.01 and p < 0. 0001, respectively). Both lysophosphatidic acid solutions significantly inc reased the amount of new epithelium in the wounds on days 1,2, and 3 (p < 0 .05). Little wound area remained on day 4, and all wounds were fully reepit helialized by day 5. Lysophosphatidic acid did not affect the number of neu trophils or macrophages present in the wound area. Our findings show that l ysophosphatidic acid increased the amount of reepithelialization in the ear ly stages of cutaneous wound healing in excisional ear wounds, without affe cting inflammatory function.