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

摘要

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.