Non-Selective Cation Channel Activity Is Required for Lysophosphatidylcholine-Induced Monocyte Migration

Lysophosphatidylcholine (LPC) is a major atherogenic lipid which stimulates the recruitment of monocytes to atherosclerotic lesions. The physiological mechanisms underlying LPC-induced monocyte migration are poorly understood. Here we demonstrate that LPC activates non-selective cation channels, which are significantly involved in LPC-induced chemotaxis of monocytes. External LPC elicited the activation of non-selective cation currents in THP-I monocytes, which occurred in a G protein and phospholipase C-independent manner. LPC-activated currents were almost completely inhibited by Gd3+, La3+, and TRAM-34. Furthermore, currents were partially reduced by either 2-aminoethoxydiphenyl borate (2-APB) or ruthenium red, while combined application of 2-APB and ruthenium red abolished LPC-activated currents. The 2-APB-sensitive current component was potentiated by flufenamic acid and Ca2+-free extracellular solution, while the ruthenium red-sensitive current component was abolished by capsazepine. This pharmacological profile suggests that LPC simultaneously activates TRPC6 and TRPVI channels in monocytes. Furthermore, in the presence of Gd3+, La3+, TRAM-34, 2-APB, ruthenium red or capsazepine, LPC-induced chemotaxis of monocytes was substantially inhibited, indicating that activation of both channel types is required for optimal migration of LPC-stimulated monocytes. Thus, ion channel inhibition may represent a powerful strategy to attenuate the progression of atherosclerosis by reducing monocyte infiltration. J. Cell. Physiol. 221: 325-334, 2009. (C) 2009 Wiley-Liss, Inc.