Nanomolar concentrations of lysophosphatidylcholine recruit monocytes and induce pro-inflammatory cytokine production in macrophages

Lysophosphatidylcholine (LPC) has been attributed a pro-inflammatory role in atherosclerosis. Cell culture studies have identified stimulation of cytokine expression and chemotaxis by micromolar (mu M) concentrations of LPC. In the present study we have investigated if LPC, in similarity with many other lipid mediators, has pro-inflammatory effects also at nanomolar (nM) concentrations. Cultured mouse bone marrow derived and RAW264.7 macrophages exposed to LPC demonstrated two peaks of increased MIP-2 release and mRNA expression; one at 0.1-10 nM and another at mu M concentrations. Both concentration ranges of LPC were also found to stimulate THP-1 monocyte chemotaxis. However, stimulation of the cells with mu M concentrations of LPC may cause cell injury as increased release of lactate dehydrogenase was observed. Our findings demonstrate two peaks of LPC-induced pro-inflammatory activity, one in the nM and one in the mu M range, and indicate that the latter may involve a stress response to lipid cytotoxicity. (c) 2008 Elsevier Inc. All rights reserved.