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http://dx.doi.org/10.4062/biomolther.2008.16.2.069

Immunomodulatory Actions of Lysophosphatidylcholine  

Hong, Chang-Won (Department of Pharmacology, Institute of Natural Medicine, Infectious Disease Medical Research Center, College of Medicine, Hallym University)
Song, Dong-Keun (Department of Pharmacology, Institute of Natural Medicine, Infectious Disease Medical Research Center, College of Medicine, Hallym University)
Publication Information
Biomolecules & Therapeutics / v.16, no.2, 2008 , pp. 69-76 More about this Journal
Abstract
Lysophosphatidylcholine (LPC) is an endogenous phospholipid. LPC has various stimulating or modulating activities on immune cells, including lymphocytes, monocytes/macrophages and neutrophils. Studies generally revealed pro-inflammatory activities of LPC, but accumulating evidence indicates that LPC has also anti-inflammatory actions. Here we summarize immunomodulatory actions of LPC.
Keywords
Lysophosphatidylcholine; Lymphocyte; Monocyte; Macrophage; Neutrophil;
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1 Jing, Q., Xin, S. M., Zhang, W. B., Wang, P., Qin, Y. W. and Pei, G. (2000). Lysophosphatidylcholine activates p38 and p42/44 mitogen-activated protein kinases in monocytic THP-1 cells, but only p38 activation is involved in its stimulated chemotaxis. Circ Res. 87(1), 52-59   DOI   ScienceOn
2 Silliman, C. C., Elzi, D. J., Ambruso, D. R., Musters, R. J., Hamiel, C., Harbeck, R. J., Paterson, A. J., Bjornsen, A. J., Wyman, T. H., Kelher, M., England, K. M., McLaughlin-Malaxecheberria, N., Barnett, C. C., Aiboshi, J. and Bannerjee, A. (2003). Lysophosphatidylcholines prime the NADPH oxidase and stimulate multiple neutrophil functions through changes in cytosolic calcium. J Leukoc Biol. 73(4), 511-524   DOI   ScienceOn
3 Yang, L. V., Radu, C. G., Wang, L., Riedinger, M. and Witte, O. N. (2005). Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A. Blood. 105(3), 1127-1134   DOI   ScienceOn
4 Han, K. H., Hong, K. H., Ko, J., Rhee, K. S., Hong, M. K., Kim, J. J., Kim, Y. H. and Park, S. J. (2004). Lysophosphatidylcholine up-regulates CXCR4 chemokine receptor expression in human CD4 T cells. Journal of Leukocyte Biology. 76(1), 195-202   DOI   ScienceOn
5 Huang, Y. H., Schafer-Elinder, L., Wu, R., Claesson, H. E. and Frostegard, J. (1999). Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. Clin Exp Immunol. 116(2), 326-331   DOI
6 Jackson, S. K., Abate, W., Parton, J., Jones, S. and Harwood, J. L. (2008). Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response. Journal of Leukocyte Biology   DOI   ScienceOn
7 Bauldry, S. A. and Wooten, R. E. (1997). Induction of cytosolic phospholipase A2 activity by phosphatidic acid and diglycerides in permeabilized human neutrophils: interrelationship between phospholipases D and A2. Biochem J. 322 (Pt 2), 353-363   DOI
8 Biffl, W. L., Carnaggio, R., Moore, E. E., Ciesla, D. J., Johnson, J. L. and Silliman, C. C. (2003). Clinically relevant hypertonicity prevents stored blood- and lipid-mediated delayed neutrophil apoptosis independent of p38 MAPK or caspase-3 activation. Surgery. 134(1), 86-91   DOI   ScienceOn
9 Lee, Y. K., Im, Y. J., Kim, Y. L. and Im, D. S. (2006). Characterization of Ca2+ influx induced by dimethylphytosphingosine and lysophosphatidylcholine in U937 monocytes. Biochem Biophys Res Commun. 348(3), 1116-1122   DOI   ScienceOn
10 Legradi, A., Chitu, V., Szukacsov, V., Fajka-Boja, R., Szekely Szucs, K. and Monostori, E. (2004). Lysophosphatidylcholine is a regulator of tyrosine kinase activity and intracellular Ca(2+) level in Jurkat T cell line. Immunol Lett. 91(1), 17-21   DOI   ScienceOn
11 Engelmann, B., Zieseniss, S., Brand, K., Page, S., Lentschat, A., Ulmer, A. J. and Gerlach, E. (1999). Tissue factor expression of human monocytes is suppressed by lysophosphatidylcholine. Arterioscler Thromb Vasc Biol. 19(1), 47-53   DOI   ScienceOn
12 Lin, P., Welch, E. J., Gao, X. P., Malik, A. B. and Ye, R. D. (2005). Lysophosphatidylcholine modulates neutrophil oxidant production through elevation of cyclic AMP. J Immunol. 174(5), 2981-2989   DOI
13 Liu-Wu, Y., Hurt-Camejo, E. and Wiklund, O. (1998). Lysophosphatidylcholine induces the production of IL-$1{\beta}$ by human monocytes. Atherosclerosis. 137(2), 351-357   DOI   ScienceOn
14 McMurray, H. F., Parthasarathy, S. and Steinberg, D. (1993). Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. J Clin Invest. 92(2), 1004-1008   DOI   ScienceOn
15 Englberger, W., Bitter-Suermann, D. and Hadding, U. (1987). Influence of lysophospholipids and PAF on the oxidative burst of PMNL. Int J Immunopharmacol. 9(3), 275-282   DOI   ScienceOn
16 Frasch, S. C., Zemski-Berry, K., Murphy, R. C., Borregaard, N., Henson, P. M. and Bratton, D. L. (2007). Lysophospholipids of different classes mobilize neutrophil secretory vesicles and induce redundant signaling through G2A. J Immunol. 178(10), 6540-6548   DOI
17 Nishi, E., Kume, N., Ochi, H., Moriwaki, H., Wakatsuki, Y., Higashiyama, S., Taniguchi, N. and Kita, T. (1997). Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T lymphocytes. Circ Res. 80(5), 638-644   DOI   ScienceOn
18 Oestvang, J., Anthonsen, M. W. and Johansen, B. (2003). Role of secretory and cytosolic phospholipase A(2) enzymes in lysophosphatidylcholine-stimulated monocyte arachidonic acid release. FEBS Lett. 555(2), 257-262   DOI   ScienceOn
19 Nishi, E., Kume, N., Ueno, Y., Ochi, H., Moriwaki, H. and Kita, T. (1998). Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes. Circ Res. 83(5), 508-515   DOI   ScienceOn
20 Nishioka, H., Horiuchi, H., Arai, H. and Kita, T. (1998). Lysophosphatidylcholine generates superoxide anions through activation of phosphatidylinositol 3-kinase in human neutrophils. FEBS Lett. 441(1), 63-66   DOI   ScienceOn
21 Kishimoto, T., Soda, Y., Matsuyama, Y. and Mizuno, K. (2002). An enzymatic assay for lysophosphatidylcholine concentration in human serum and plasma. Clin Biochem. 35(5), 411- 416   DOI   ScienceOn
22 Lauber, K., Bohn, E., Krober, S. M., Xiao, Y. J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., Xu, Y., Autenrieth, I. B., Schulze-Osthoff, K., Belka, C., Stuhler, G. and Wesselborg, S. (2003). Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell. 113(6), 717-730   DOI   ScienceOn
23 Lee, H. Y., Kang, H. K., Yoon, H. R., Kwak, J. Y. and Bae, Y. S. (2004). Lysophosphatidic acid is a mediator of Trp-Lys-Tyr- Met-Val-d-Met-induced calcium influx. Biochem Biophys Res Commun. 324(1), 458-465   DOI   ScienceOn
24 Parks, B. W., Gambill, G. P., Lusis, A. J. and Kabarowski, J. H. (2005). Loss of G2A promotes macrophage accumulation in atherosclerotic lesions of low density lipoprotein receptor-deficient mice. J Lipid Res. 46(7), 1405-1415   DOI   ScienceOn
25 Murch, O., Collin, M., Sepodes, B., Foster, S. J., Mota-Filipe, H. and Thiemermann, C. (2006). Lysophosphatidylcholine reduces the organ injury and dysfunction in rodent models of gramnegative and gram-positive shock. Br J Pharmacol. 148(6), 769-777   DOI   ScienceOn
26 Perrin-Cocon, L., Agaugue, S., Coutant, F., Saint-Mezard, P., Guironnet-Paquet, A., Nicolas, J. F., Andre, P. and Lotteau, V. (2006). Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses. Vaccine. 24(9), 1254-1263   DOI   ScienceOn
27 Peter, C., Waibel, M., Radu, C. G., Yang, L. V., Witte, O. N., Schulze-Osthoff, K., Wesselborg, S. and Lauber, K. (2008). Migration to apoptotic 'find-me' signals is mediated via the phagocyte receptor G2A. J Biol Chem. 283(9), 5296-5305   DOI   ScienceOn
28 MUller, J., Petkovi, M., Schiller, J., Arnold, K., Reichl, S. and Arnhold, J. (2002). Effects of lysophospholipids on the generation of reactive oxygen species by fMLP- and PMA-stimulated human neutrophils. Luminescence : the journal of biological and chemical luminescence. 17(3), 141-149   DOI   ScienceOn
29 Nakano, T., Raines, E. W., Abraham, J. A., Klagsbrun, M. and Ross, R. (1994). Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes. Proc Natl Acad Sci USA. 91(3), 1069-1073   DOI   ScienceOn
30 Ngwenya, B. Z. and Yamamoto, N. (1985). Activation of peritoneal macrophages by lysophosphatidylcholine. Biochim Biophys Acta. 839(1), 9-15   DOI   ScienceOn
31 Ryborg, A. K., Deleuran, B., Thestrup-Pedersen, K. and Kragballe, K. (1994). Lysophosphatidylcholine: a chemoattractant to human T lymphocytes. Arch Dermatol Res. 286(8), 462-465   DOI
32 Okajima, F., Sato, K., Tomura, H., Kuwabara, A., Nochi, H., Tamoto, K., Kondo, Y., Tokumitsu, Y. and Ui, M. (1998). Stimulatory and inhibitory actions of lysophosphatidylcholine, depending on its fatty acid residue, on the phospholipase C/ Ca2+ system in HL-60 leukaemia cells. Biochem J. 336 (Pt 2), 491-500   DOI
33 Sakai, M., Miyazaki, A., Hakamata, H., Sasaki, T., Yui, S., Yamazaki, M., Shichiri, M. and Horiuchi, S. (1994). Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages. J Biol Chem. 269(50), 31430-31435
34 Sakata-Kaneko, S., Wakatsuki, Y., Usui, T., Matsunaga, Y., Itoh, T., Nishi, E., Kume, N. and Kita, T. (1998). Lysophosphatidylcholine upregulates CD40 ligand expression in newly activated human CD4+ T cells. FEBS Lett. 433(1-2), 161-165   DOI   ScienceOn
35 Ogita, T., Tanaka, Y., Nakaoka, T., Matsuoka, R., Kira, Y., Nakamura, M., Shimizu, T. and Fujita, T. (1997). Lysophosphatidylcholine transduces Ca2+ signaling via the platelet-activating factor receptor in macrophages. Am J Physiol. 272(1 Pt 2), H17-24
36 Olofsson, K. E., Andersson, L., Nilsson, J. and Björkbacka, H. (2008). Nanomolar concentrations of lysophosphatidylcholine recruit monocytes and induce pro-inflammatory cytokine production in macrophages. Biochem Biophys Res Commun. 370(2), 348-352   DOI   ScienceOn
37 Ousman, S. S. and David, S. (2000). Lysophosphatidylcholine induces rapid recruitment and activation of macrophages in the adult mouse spinal cord. Glia. 30(1), 92-104   DOI   ScienceOn
38 Taylor, L. A., Arends, J., Hodina, A. K., Unger, C. and Massing, U. (2007). Plasma lyso-phosphatidylcholine concentration is decreased in cancer patients with weight loss and activated inflammatory status. Lipids in health and disease. 6, 17   DOI   ScienceOn
39 Weng, Z., Fluckiger, A. C., Nisitani, S., Wahl, M. I., Le, L. Q., Hunter, C. A., Fernal, A. A., Le Beau, M. M. and Witte, O. N. (1998). A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M. Proc Natl Acad Sci U S A. 95(21), 12334-12339   DOI
40 Weber, C., Erl, W. and Weber, P. C. (1995). Enhancement of monocyte adhesion to endothelial cells by oxidatively modified low-density lipoprotein is mediated by activation of CD11b. Biochem Biophys Res Commun. 206(2), 621-628   DOI   ScienceOn
41 Quinn, M. T., Parthasarathy, S. and Steinberg, D. (1988). Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis. Proc Natl Acad Sci U S A. 85(8), 2805-2809   DOI   ScienceOn
42 Radu, C. G., Yang, L. V., Riedinger, M., Au, M. and Witte, O. N. (2004). T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc Natl Acad Sci U S A. 101(1), 245- 250   DOI   ScienceOn
43 Rikitake, Y., Hirata, K., Yamashita, T., Iwai, K., Kobayashi, S., Itoh, H., Ozaki, M., Ejiri, J., Shiomi, M., Inoue, N., Kawashima, S. and Yokoyama, M. (2002). Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 22(12), 2049-2053   DOI   ScienceOn
44 Ryborg, A. K., Deleuran, B., Sogaard, H. and Kragballe, K. (2000). Intracutaneous injection of lysophosphatidylcholine induces skin inflammation and accumulation of leukocytes. Acta Derm Venereol. 80(4), 242-246   DOI
45 Schilling, T., Lehmann, F., Rückert, B. and Eder, C. (2004). Physiological mechanisms of lysophosphatidylcholine-induced de-ramification of murine microglia. J Physiol (Lond). 557(Pt 1), 105-120   DOI   ScienceOn
46 Yuan, Y., Schoenwaelder, S. M., Salem, H. H. and Jackson, S. P. (1996). The bioactive phospholipid, lysophosphatidylcholine, induces cellular effects via G-protein-dependent activation of adenylyl cyclase. J Biol Chem. 271(43), 27090-27098   DOI   ScienceOn
47 Yun, M. R., Okajima, F. and Im, D. S. (2004). The action mode of lysophosphatidylcholine in human monocytes. J Pharmacol Sci. 94(1), 45-50   DOI   ScienceOn
48 Zhu, X., Learoyd, J., Butt, S., Zhu, L., Usatyuk, P. V., Natarajan, V., Munoz, N. M. and Leff, A. R. (2007). Regulation of eosinophil adhesion by lysophosphatidylcholine via a non-storeoperated Ca2+ channel. Am J Respir Cell Mol Biol. 36(5), 585-593   DOI   ScienceOn
49 Schmid, B., Finnen, M. J., Harwood, J. L. and Jackson, S. K. (2003). Acylation of lysophosphatidylcholine plays a key role in the response of monocytes to lipopolysaccharide. Eur J Biochem. 270(13), 2782-2788   DOI   ScienceOn
50 Silliman, C. C., Clay, K. L., Thurman, G. W., Johnson, C. A. and Ambruso, D. R. (1994). Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 124(5), 684-694
51 Silliman, C. C., Dickey, W. O., Paterson, A. J., Thurman, G. W., Clay, K. L., Johnson, C. A. and Ambruso, D. R. (1996). Analysis of the priming activity of lipids generated during routine storage of platelet concentrates. Transfusion. 36(2), 133-139   DOI   ScienceOn
52 Yamamoto, N. and Naraparaju, V. R. (1996). Role of vitamin D3- binding protein in activation of mouse macrophages. J Immunol. 157(4), 1744-1749
53 Wilson-Ashworth, H. A., Judd, A. M., Law, R. M., Freestone, B. D., Taylor, S., Mizukawa, M. K., Cromar, K. R., Sudweeks, S. and Bell, J. D. (2004). Formation of transient non-protein calcium pores by lysophospholipids in S49 Lymphoma cells. J Membr Biol. 200(1), 25-33   DOI
54 Wyman, T. H., Bjornsen, A. J., Elzi, D. J., Smith, C. W., England, K. M., Kelher, M. and Silliman, C. C. (2002). A two-insult in vitro model of PMN-mediated pulmonary endothelial damage: requirements for adherence and chemokine release. Am J Physiol Cell Physiol. 283(6), C1592-1603   DOI   ScienceOn
55 Yamamoto, M., Hara, H. and Adachi, T. (2002). The expression of extracellular-superoxide dismutase is increased by lysophosphatidylcholine in human monocytic U937 cells. Atherosclerosis. 163(2), 223-228   DOI   ScienceOn
56 Yan, J. J., Jung, J. S., Lee, J. E., Lee, J., Huh, S. O., Kim, H. S., Jung, K. C., Cho, J. Y., Nam, J. S., Suh, H. W., Kim, Y. H. and Song, D. K. (2004). Therapeutic effects of lysophosphatidylcholine in experimental sepsis. Nat Med. 10(2), 161-167   DOI   ScienceOn
57 Chen, G., Li, J., Qiang, X., Czura, C. J., Ochani, M., Ochani, K., Ulloa, L., Yang, H., Tracey, K. J., Wang, P., Sama, A. E. and Wang, H. (2005). Suppression of HMGB1 release by stearoyl lysophosphatidylcholine:an additional mechanism for its therapeutic effects in experimental sepsis. J Lipid Res. 46(4), 623-627   DOI   ScienceOn
58 Zurgil, N., Afrimzon, E., Shafran, Y., Shovman, O., Gilburd, B., Brikman, H., Shoenfeld, Y. and Deutsch, M. (2007). Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis. Atherosclerosis. 190(1), 73-83   DOI   ScienceOn
59 Asaoka, Y., Oka, M., Yoshida, K. and Nishizuka, Y. (1991). Lysophosphatidylcholine as a possible second messenger synergistic to diacylglycerol and calcium ion for T-lymphocyte activation. Biochem Biophys Res Commun. 178(3), 1378- 1385   DOI   ScienceOn
60 Asaoka, Y., Oka, M., Yoshida, K., Sasaki, Y. and Nishizuka, Y. (1992). Role of lysophosphatidylcholine in T-lymphocyte activation: involvement of phospholipase A2 in signal transduction through protein kinase C. Proc Natl Acad Sci USA. 89(14), 6447-6451   DOI   ScienceOn
61 Drobnik, W., Liebisch, G., Audebert, F. X., Frohlich, D., Gluck, T., Vogel, P., Rothe, G. and Schmitz, G. (2003). Plasma ceramide and lysophosphatidylcholine inversely correlate with mortality in sepsis patients. J Lipid Res. 44(4), 754-761   DOI   ScienceOn
62 Coutant, F., Agaugue, S., Perrin-Cocon, L., Andre, P. and Lotteau, V. (2004). Sensing environmental lipids by dendritic cell modulates its function. J Immunol. 172(1), 54-60   DOI
63 Coutant, F., Perrin-Cocon, L., Agaugué, S., Delair, T., Andre, P. and Lotteau, V. (2002). Mature dendritic cell generation promoted by lysophosphatidylcholine. J Immunol. 169(4), 1688- 1695   DOI
64 De Vries, H. E., Ronken, E., Reinders, J. H., Buchner, B., Van Berkel, T. J. and Kuiper, J. (1998). Acute effects of oxidized low density lipoprotein on metabolic responses in macrophages. FASEB J. 12(1), 111-118   DOI
65 Ginsburg, I., Ward, P. A. and Varani, J. (1989). Lysophosphatides enhance superoxide responses of stimulated human neutrophils. Inflammation. 13(2), 163-174   DOI
66 Gomez-Munoz, A., O'Brien, L., Hundal, R. and Steinbrecher, U. P. (1999). Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages. J Lipid Res. 40(6), 988-993