Expression and Function of Lysophosphatidic Acid Receptors in Cultured Rodent Microglial Cells

Microglia are the resident tissue macrophages of the central nervous system. They are rapidly activated by a variety of insults; and recently, receptors linked to cytoplasmic Ca²⁺ signals have been implicated in such events. One potential class of receptors are those recognizing lysophosphatidic acid (LPA). LPA is a phospholipid signaling molecule that has been shown to cause multiple cellular responses, including increases in cytoplasmic calcium. We examined whether any of the known LPA receptor genes (lp_A1/Edg2, lp_A2/Edg4, and lp_A3/Edg7) are expressed by cultured mouse or rat microglia. Reverse transcriptase-polymerase chain reaction indicated that mouse microglia predominantly expressed the lP_A1 gene, whereas rat microglia predominantly expressed lP _A3. Although LPA induced increases in the cytoplasmic Ca ²⁺ concentration in both microglial preparations, the responses differed substantially. The Ca²⁺ signal in rat microglia occurred primarily through Ca²⁺ influx via the plasma membrane, whereas the Ca²⁺ signal in mouse microglia was due to release from intracellular stores. Only at high concentrations was an additional influx component recruited. Additionally, LPA induced increased metabolic activity in mouse (but not rat) microglial cells. Our findings provide evidence for functional LPA receptors on microglia. Thus, LPA might play an important role as a mediator of microglial activation in response to central nervous system injury.