Abstract
Native low density lipoprotein (LDL) does not affect monocyte/macrophage motility. On the other hand, oxidatively modified LDL inhibits the motility of resident peritoneal macrophages yet acts as a chemotactic factor for circulating human monocytes. We now show that lysophosphatidylcholine (lyso-PtdCho), which is generated by a phospholipase A2 activity during LDL oxidation, is a potent chemotactic factor for monocytes. It is not chemotactic for neutrophils or for resident macrophages. Platelet-activating factor, after treatment with phospholipase A2, becomes chemotactic for monocytes, whereas the intact factor is not. Synthetic 1-palmitoyl-lyso-PtdCho showed chemotactic activity comparable to that of the lyso-PtdCho fraction derived from oxidized LDL. The results suggest that lyso-PtdCho in oxidized LDL may favor recruitment of monocytes into the arterial wall during the early stages of atherogenesis. Generation of lyso-PtdCho, either from LDL itself or from membrane phospholipids of damaged cells, could play a more general role in inflammatory processes throughout the body.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aqel N. M., Ball R. Y., Waldmann H., Mitchinson M. J. Monocytic origin of foam cells in human atherosclerotic plaques. Atherosclerosis. 1984 Dec;53(3):265–271. doi: 10.1016/0021-9150(84)90127-8. [DOI] [PubMed] [Google Scholar]
- BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- Basu S. K., Goldstein J. L., Anderson G. W., Brown M. S. Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3178–3182. doi: 10.1073/pnas.73.9.3178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berliner J. A., Territo M., Almada L., Carter A., Shafonsky E., Fogelman A. M. Monocyte chemotactic factor produced by large vessel endothelial cells in vitro. Arteriosclerosis. 1986 May-Jun;6(3):254–258. doi: 10.1161/01.atv.6.3.254. [DOI] [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
- Buonassisi V., Venter J. C. Hormone and neurotransmitter receptors in an established vascular endothelial cell line. Proc Natl Acad Sci U S A. 1976 May;73(5):1612–1616. doi: 10.1073/pnas.73.5.1612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- COHN Z. A., BENSON B. THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY. J Exp Med. 1965 Jan 1;121:153–170. doi: 10.1084/jem.121.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carew T. E., Schwenke D. C., Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7725–7729. doi: 10.1073/pnas.84.21.7725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cathcart M. K., Morel D. W., Chisolm G. M., 3rd Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J Leukoc Biol. 1985 Aug;38(2):341–350. doi: 10.1002/jlb.38.2.341. [DOI] [PubMed] [Google Scholar]
- Ferrante A., Thong Y. H. Optimal conditions for simultaneous purification of mononuclear and polymorphonuclear leucocytes from human blood by the Hypaque-Ficoll method. J Immunol Methods. 1980;36(2):109–117. doi: 10.1016/0022-1759(80)90036-8. [DOI] [PubMed] [Google Scholar]
- Gerrity R. G., Goss J. A., Soby L. Control of monocyte recruitment by chemotactic factor(s) in lesion-prone areas of swine aorta. Arteriosclerosis. 1985 Jan-Feb;5(1):55–66. doi: 10.1161/01.atv.5.1.55. [DOI] [PubMed] [Google Scholar]
- Gerrity R. G. The role of the monocyte in atherogenesis: II. Migration of foam cells from atherosclerotic lesions. Am J Pathol. 1981 May;103(2):191–200. [PMC free article] [PubMed] [Google Scholar]
- Goetzl E. J., Derian C. K., Tauber A. I., Valone F. H. Novel effects of 1-O-hexadecyl-2-acyl-sn-glycero-3-phosphorycholine mediators on human leukocyte function: delineation of the specific roles of the acyl substituents. Biochem Biophys Res Commun. 1980 Jun 16;94(3):881–888. doi: 10.1016/0006-291x(80)91317-0. [DOI] [PubMed] [Google Scholar]
- HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heinecke J. W., Baker L., Rosen H., Chait A. Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells. J Clin Invest. 1986 Mar;77(3):757–761. doi: 10.1172/JCI112371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heinecke J. W., Rosen H., Chait A. Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest. 1984 Nov;74(5):1890–1894. doi: 10.1172/JCI111609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis. 1983 Mar-Apr;3(2):149–159. doi: 10.1161/01.atv.3.2.149. [DOI] [PubMed] [Google Scholar]
- Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6499–6503. doi: 10.1073/pnas.78.10.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6499–6503. doi: 10.1073/pnas.78.10.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henriksen T., Mahoney E. M., Steinberg D. Interactions of plasma lipoproteins with endothelial cells. Ann N Y Acad Sci. 1982;401:102–116. doi: 10.1111/j.1749-6632.1982.tb25711.x. [DOI] [PubMed] [Google Scholar]
- Hessler J. R., Robertson A. L., Jr, Chisolm G. M., 3rd LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture. Atherosclerosis. 1979 Mar;32(3):213–229. doi: 10.1016/0021-9150(79)90166-7. [DOI] [PubMed] [Google Scholar]
- Hoffman R. D., Kligerman M., Sundt T. M., Anderson N. D., Shin H. S. Stereospecific chemoattraction of lymphoblastic cells by gradients of lysophosphatidylcholine. Proc Natl Acad Sci U S A. 1982 May;79(10):3285–3289. doi: 10.1073/pnas.79.10.3285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jauchem J. R., Lopez M., Sprague E. A., Schwartz C. J. Mononuclear cell chemoattractant activity from cultured arterial smooth muscle cells. Exp Mol Pathol. 1982 Oct;37(2):166–174. doi: 10.1016/0014-4800(82)90033-8. [DOI] [PubMed] [Google Scholar]
- Kumagai K., Itoh K., Hinuma S., Tada M. Pretreatment of plastic Petri dishes with fetal calf serum. A simple method for macrophage isolation. J Immunol Methods. 1979;29(1):17–25. doi: 10.1016/0022-1759(79)90121-2. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Mazzone T., Jensen M., Chait A. Human arterial wall cells secrete factors that are chemotactic for monocytes. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5094–5097. doi: 10.1073/pnas.80.16.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morel D. W., DiCorleto P. E., Chisolm G. M. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis. 1984 Jul-Aug;4(4):357–364. doi: 10.1161/01.atv.4.4.357. [DOI] [PubMed] [Google Scholar]
- Parthasarathy S., Printz D. J., Boyd D., Joy L., Steinberg D. Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor. Arteriosclerosis. 1986 Sep-Oct;6(5):505–510. doi: 10.1161/01.atv.6.5.505. [DOI] [PubMed] [Google Scholar]
- Parthasarathy S., Steinbrecher U. P., Barnett J., Witztum J. L., Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 May;82(9):3000–3004. doi: 10.1073/pnas.82.9.3000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Portman O. W., Alexander M. Lysophosphatidylcholine concentrations and metabolism in aortic intima plus inner media: effect of nutritionally induced atherosclerosis. J Lipid Res. 1969 Mar;10(2):158–165. [PubMed] [Google Scholar]
- Quinn M. T., Parthasarathy S., Fong L. G., Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci U S A. 1987 May;84(9):2995–2998. doi: 10.1073/pnas.84.9.2995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quinn M. T., Parthasarathy S., Steinberg D. Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5949–5953. doi: 10.1073/pnas.82.17.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rand R. P., Pangborn W. A., Purdon A. D., Tinker D. O. Lysolecithin and cholesterol interact stoichiometrically forming bimolecular lamellar structures in the presence of excess water, of lysolecithin or cholesterol. Can J Biochem. 1975 Feb;53(2):189–195. doi: 10.1139/o75-027. [DOI] [PubMed] [Google Scholar]
- Raymond T. L., Reynolds S. A. Lipoproteins of the extravascular space: alterations in low density lipoproteins of interstitial inflammatory fluid. J Lipid Res. 1983 Feb;24(2):113–119. [PubMed] [Google Scholar]
- Rosenfeld M. E., Tsukada T., Gown A. M., Ross R. Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis. 1987 Jan-Feb;7(1):9–23. doi: 10.1161/01.atv.7.1.9. [DOI] [PubMed] [Google Scholar]
- Schaffner T., Taylor K., Bartucci E. J., Fischer-Dzoga K., Beeson J. H., Glagov S., Wissler R. W. Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. Am J Pathol. 1980 Jul;100(1):57–80. [PMC free article] [PubMed] [Google Scholar]
- Schiffmann E., Corcoran B. A., Wahl S. M. N-formylmethionyl peptides as chemoattractants for leucocytes. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1059–1062. doi: 10.1073/pnas.72.3.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw J. O., Pinckard R. N., Ferrigni K. S., McManus L. M., Hanahan D. J. Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine (platelet activating factor). J Immunol. 1981 Sep;127(3):1250–1255. [PubMed] [Google Scholar]
- Snyderman R., Pike M. C. Chemoattractant receptors on phagocytic cells. Annu Rev Immunol. 1984;2:257–281. doi: 10.1146/annurev.iy.02.040184.001353. [DOI] [PubMed] [Google Scholar]
- Steinbrecher U. P., Parthasarathy S., Leake D. S., Witztum J. L., Steinberg D. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3883–3887. doi: 10.1073/pnas.81.12.3883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeda A., Palfree R. G., Forsdyke D. R. Role of serum in inhibition of cultured lymphocytes by lysophosphatidylcholine. Biochim Biophys Acta. 1982 Jan 15;710(1):87–98. doi: 10.1016/0005-2760(82)90194-1. [DOI] [PubMed] [Google Scholar]
- Vadas P., Stefanski E., Pruzanski W. Characterization of extracellular phospholipase A2 in rheumatoid synovial fluid. Life Sci. 1985 Feb 11;36(6):579–587. doi: 10.1016/0024-3205(85)90640-x. [DOI] [PubMed] [Google Scholar]
- Wardlaw A. J., Moqbel R., Cromwell O., Kay A. B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986 Dec;78(6):1701–1706. doi: 10.1172/JCI112765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watanabe T., Hirata M., Yoshikawa Y., Nagafuchi Y., Toyoshima H., Watanabe T. Role of macrophages in atherosclerosis. Sequential observations of cholesterol-induced rabbit aortic lesion by the immunoperoxidase technique using monoclonal antimacrophage antibody. Lab Invest. 1985 Jul;53(1):80–90. [PubMed] [Google Scholar]
- Weltzien H. U. Cytolytic and membrane-perturbing properties of lysophosphatidylcholine. Biochim Biophys Acta. 1979 Aug 20;559(2-3):259–287. doi: 10.1016/0304-4157(79)90004-2. [DOI] [PubMed] [Google Scholar]