Regulation of inflammatory responses by oxidized phospholipids: structure-function relationships

Increasing evidence points to the role of oxidized phospholipids as modulators of inflammatory processes. These modified phospholipids are derived from lipoproteins or cellular membranes and accumulate at sites of inflammation such as atherosclerotic lesions. It has been shown that oxidized phospholipids influence a variety of cellular functions such as chemokine production and expression of adhesion molecules. Furthermore, recent reports indicate that oxidized phospholipids act as ligands for pattern-recognition receptors which detect conserved pathogen-associated molecular patterns during innate immune defense. Thus, the diversity of individual phospholipid oxidation products reflects the many aspects of the inflammatory process they influence. In this review, we focus on structural features used to classify different oxidized phospholipids and how they relate to specific biological responses. As the chemical identification of oxidized phospholipid products proceeds, distinctive structural motifs emerge that can help us to understand the mechanism of action of these unique compounds and how to intervene for therapeutic purposes.