Despite overlapping structural aspects with other
phospholipids,
lysophosphatidylserine (lysoPS), the monoacyl derivative of
phosphatidylserine (diacylPS), appears to exert unique signaling characteristics important in both the early stages of initiating acute
inflammation and in the orchestration of its resolution. LysoPS has long been known as a signaling
phospholipid in mast cell biology, markedly enhancing stimulated histamine release and
eicosanoid production. More recently, there has been a resurgence of interest in lysoPS as new roles in the promotion of phagocytosis of apoptotic cells, so-called efferocytosis, and resolution of
inflammation have been identified. With regard to the latter, lysoPS generated in/on activated or aged apoptotic neutrophils enhances their clearance by macrophages via signaling through the macrophage
G-protein coupled receptor G2A. In macrophages, this early acting pathway results in PKA-dependent augmentation of Rac1 activity via increased production of PGE₂ and cAMP. As such, macrophages stimulated with lysoPS demonstrate significantly increased efferocytic capacity necessary to clear large numbers of recruited neutrophils typical of acute
inflammation. Given that clearance of these cells is critical for restoration of tissue function, lysoPS, as a pro-resolving
lipid mediator, is hypothesized to play a key role in promoting timely resolution of
inflammation. This article will review our current knowledge of lysoPS biology including receptor signaling and mechanisms of generation as well as summarize the more recent evidence of its expanding roles in
inflammation.