The G protein-coupled receptor (GPCR), G2A, was originally identified by Owen Witte’s group as a transcriptional target of the human leukemogenic tyrosine kinase, BCR-ABL, in murine bone marrow B lymphoid progenitor cells ( 17). This review discusses these immunoregulatory properties of LPC with focus on the role of the G2A receptor and its potential involvement in chronic inflammatory and autoimmune disease. However, other potentially influential functions of G2A not ascribed to any specific lipid ligand have been revealed in studies with G2A deficient mice, including the regulation of lipoprotein-cholesterol metabolism. These LPC-dependent effects of G2A may contribute to mechanisms controlling the initiation or resolution of inflammation in response to infection and may also modify the susceptibility to sepsis and chronic inflammatory autoimmune disease by facilitating the efficient clearance of bacterial pathogens and apoptotic cells respectively. Recent studies have demonstrated an important role for the G protein-coupled receptor (GPCR), G2A, in mediating cellular responses to LPC capable of modulating macrophage and T cell migration ( 10, 11), neutrophil and macrophage activation ( 12– 15), and phagocytic clearance of apoptotic cells and activated neutrophils ( 14, 16). LPC is also considered to be an etiological factor in certain chronic inflammatory diseases, including atherosclerosis and the autoimmune disease systemic lupus erythematosus (SLE), in which local and systemic increases in LPC levels are a characteristic feature ( 6– 9). Based almost exclusively on studies of LPC effects on cultured cells, LPC thus generated is thought to influence the function of immunoregulatory cells to modulate inflammatory processes and immune responses. The potentiation of secretory PLA 2 (sPLA 2) activity and the oxidative modification of cell membrane and lipoprotein phospholipids contribute to significant increases in local and circulating levels of LPC and oxidized fatty acids during inflammation and under conditions of oxidative stress ( 4, 5). The production of LPC by phospholipase A 2 (PLA 2)-mediated phosphatidylcholine (PC) hydrolysis, coupled to its re-acylation by LPC-acyltransferases (LPC-ATs), plays an important role in cellular phospholipid homeostasis, maintaining an adequate supply of fatty acid precursors for the generation of important lipid mediators in response to inflammation ( 2, 3). Lysophosphatidylcholine (LPC) is a highly abundant bioactive lysolipid present at high concentrations in the circulation where it is predominantly associated with albumin and lipoproteins ( 1).
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