Expression of the lysophospholipid receptor family and investigation of lysophospholipid-mediated responses in human macrophages

Abstract

Some of the biological effects of lipoproteins have been attributed to their association with lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC). These lysophospholipids mediate multiple biological responses via several G protein-coupled receptors (GPR). The expression of these receptors, however, has not been systematically investigated in primary human monocytes and macrophages as major cells involved in atherosclerosis. The mRNAs for all 15 receptors described so far were detected in monocytes, macrophages, foam cells and high density lipoprotein (HDL 3)-treated cells using real time RT-PCR. Immunoblots revealed that S1P 1, S1P 2, S1P 4, LPA 1, LPA 2 and GPR65 are expressed in monocytes and macrophages, while S1P 5 and LPA 3 have not been detected. S1P 3 was induced during differentiation but down-regulated by lipid-loading and HDL 3, whereas LPA 1 was down-regulated in differentiated macrophages. The influence of S1P on macrophages was investigated and the induction of CD32 indicates an enhanced phagocytic activity. Altogether, these data give insights into the expression and regulation of lysophospholipid receptors in primary human monocytes, macrophages and foam cells.