Lysophosphatidylcholine‐induced mitochondrial ROS formation and activation of AMPK promote macrophage chemotaxis and efferocytosis

Abstract

Clearance of apoptotic cells is a critical step for efficient resolution of inflammatory conditions, including those resulted from acute lung injury (ALI). Lysophosphatidylcholine (LysoPC) is a bioactive phospholipid enriched in apoptotic cells that is known to induce migration “find me” signaling followed by macrophage phagocytosis. However, intracellular signaling pathways responsible for initiation of chemotaxis and efferocytosis by LysoPC remain to be determined. Here we demonstrated that LysoPC‐mediated increased production of mitochondrial reactive oxygen species (ROS) was associated with activation of AMPK in macrophages. AMPK inhibitor, compound C or antioxidant approach diminished both migration and engulfment of apoptotic cells. Application of G2A blocking antibody did not prevent activation of AMPK, suggesting that LysoPC‐induced AMPK activation was independent from signaling initiated by G2A receptor, but due to mitochondrial ROS. Taken together, our results revealed that AMPK activation is initial step in LysoPC mediated “find me” and “eat me” signaling pathway that requires formation of mitochondrial ROS.