Modulation of Hexadecyl-LPA-Mediated Activation of Mast Cells and Microglia by a Chemical Probe for LPA5

Mast cells and microglia play a critical role in innate immunity and inflammation and can be activated by a wide range of endogenous and exogenous stimuli. Lysophosphatidic acid (LPA) has recently been reported to activate mast cells and microglia. Using the human mast cell line HMC‐1 and the mouse microglia cell line BV‐2, we show that LPA‐mediated activation can be prevented by blockade of the LPA receptor 5 (LPA5) in both cell lines. The identification of new LPA5‐specific antagonists as tool compounds to probe and modulate the LPA5/LPA axis in relevant in vitro and in vivo assays should contribute to better understanding of the underlying role of LPAs in the development and progression of (neuro‐) inflammatory diseases. Phospholipids and inflammation: Mast cells and microglia can be activated by hexadecyllysophosphatidic acid (hexadecyl‐LPA) through LPA receptor 5 (LPA5). Inhibition of the hexadecyl‐LPA5/LPA axis by a LPA5 antagonist could provide new insights into the role of these cell types in inflammation and innate immunity.