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. 1990 Mar;136(3):609–621.

Macrophage secretory products selectively stimulate dermatan sulfate proteoglycan production in cultured arterial smooth muscle cells.

I J Edwards 1, W D Wagner 1, R T Owens 1
PMCID: PMC1877497  PMID: 2316626

Abstract

Arterial dermatan sulfate proteoglycan has been shown to increase with atherosclerosis progression, but factors responsible for this increase are unknown. To test the hypothesis that smooth muscle cell proteoglycan synthesis may be modified by macrophage products, pigeon arterial smooth muscle cells were exposed to the media of either cholesteryl ester-loaded pigeon peritoneal macrophages or a macrophage cell line P388D1. Proteoglycans radiolabeled with [35S]sulfate and [3H]serine were isolated from culture media and smooth muscle cells and purified following precipitation with 1-hexadecylpyridinium chloride and chromatography. Increasing concentrations of macrophage-conditioned media were associated with a dose-response increase in [35S]sulfate incorporation into secreted proteoglycans, but there was no change in cell-associated proteoglycans. Incorporation of [3H]serine into total proteoglycan core proteins was not significantly different (5.2 X 10(5) dpm and 5.5 X 10(5) disintegrations per minute (dpm) in control and conditioned media-treated cultures, respectively), but selective effects were observed on individual proteoglycan types. Twofold increases in dermatan sulfate proteoglycan and limited degradation of chondroitin sulfate proteoglycan were apparent based on core proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoinhibition studies indicated that interleukin-1 was involved in the modulation of proteoglycan synthesis by macrophage-conditioned media. These data provide support for the role of macrophages in alteration of the matrix proteoglycans synthesized by smooth muscle cells and provide a mechanism to account for the reported increased dermatan sulfate/chondroitin sulfate ratios in the developing atherosclerotic lesion.

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Selected References

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  1. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bassols A., Massagué J. Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J Biol Chem. 1988 Feb 25;263(6):3039–3045. [PubMed] [Google Scholar]
  3. Berberian P. A., Ziboh V. A., Hsia S. L. Prostaglandin E2 biosynthesis: changes in rabbit aorta and skin during experimental atherogenesis. J Lipid Res. 1976 Jan;17(1):46–52. [PubMed] [Google Scholar]
  4. Chen J. K., Hoshi H., McKeehan W. L. Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5287–5291. doi: 10.1073/pnas.84.15.5287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christner J. E. Biosynthesis of chondroitin sulfate proteoglycan by P388D1 macrophage-like cell line. Arteriosclerosis. 1988 Sep-Oct;8(5):535–543. doi: 10.1161/01.atv.8.5.535. [DOI] [PubMed] [Google Scholar]
  6. Daireaux M., Penfornis H., Langris M., Bocquet J., Pujol J. P., Beliard R., Loyau G. Effect of a mononuclear cell culture medium on collagen and glycosaminoglycan production by synovial cells in culture. FEBS Lett. 1981 Sep 14;132(1):93–97. doi: 10.1016/0014-5793(81)80435-8. [DOI] [PubMed] [Google Scholar]
  7. Edwards I. J., Wagner W. D. Distinct synthetic and structural characteristics of proteoglycans produced by cultured artery smooth muscle cells of atherosclerosis-susceptible pigeons. J Biol Chem. 1988 Jul 15;263(20):9612–9620. [PubMed] [Google Scholar]
  8. Faggiotto A., Ross R. Studies of hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis. 1984 Jul-Aug;4(4):341–356. doi: 10.1161/01.atv.4.4.341. [DOI] [PubMed] [Google Scholar]
  9. Fowler S., Shio H., Haley N. J. Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. IV. Investigation of macrophage-like properties of aortic cell populations. Lab Invest. 1979 Oct;41(4):372–378. [PubMed] [Google Scholar]
  10. Gerrity R. G., Naito H. K., Richardson M., Schwartz C. J. Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages. Am J Pathol. 1979 Jun;95(3):775–792. [PMC free article] [PubMed] [Google Scholar]
  11. Heino J., Kähäri V. M., Mauviel A., Krusius T. Human recombinant interleukin-1 regulates cellular mRNA levels of dermatan sulphate proteoglycan core protein. Biochem J. 1988 May 15;252(1):309–312. doi: 10.1042/bj2520309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  13. Iverius P. H. The interaction between human plasma lipoproteins and connective tissue glycosaminoglycans. J Biol Chem. 1972 Apr 25;247(8):2607–2613. [PubMed] [Google Scholar]
  14. Jerome W. G., Lewis J. C. Early atherogenesis in White Carneau pigeons. II. Ultrastructural and cytochemical observations. Am J Pathol. 1985 May;119(2):210–222. [PMC free article] [PubMed] [Google Scholar]
  15. Joris I., Zand T., Nunnari J. J., Krolikowski F. J., Majno G. Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol. 1983 Dec;113(3):341–358. [PMC free article] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Libby P., Warner S. J., Friedman G. B. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest. 1988 Feb;81(2):487–498. doi: 10.1172/JCI113346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Libby P., Wyler D. J., Janicka M. W., Dinarello C. A. Differential effects of human interleukin-1 on growth of human fibroblasts and vascular smooth muscle cells. Arteriosclerosis. 1985 Mar-Apr;5(2):186–191. doi: 10.1161/01.atv.5.2.186. [DOI] [PubMed] [Google Scholar]
  19. Mizel S. B., Oppenheim J. J., Rosentreich D. L. Characterization of lymphocyte-activating factor (LAF) produced by a macrophage cell line, P388D1. II. Biochemical characterization of LAF induced by activated T cells and LPS. J Immunol. 1978 May;120(5):1504–1508. [PubMed] [Google Scholar]
  20. Pasternak R. D., Hubbs S. J., Caccese R. G., Marks R. L., Conaty J. M., DiPasquale G. Interleukin-1 stimulates the secretion of proteoglycan- and collagen-degrading proteases by rabbit articular chondrocytes. Clin Immunol Immunopathol. 1986 Dec;41(3):351–367. doi: 10.1016/0090-1229(86)90006-1. [DOI] [PubMed] [Google Scholar]
  21. Pietilä K., Moilanen T., Nikkari T. Prostaglandins enhance the synthesis of glycosaminoglycans and inhibit the growth of rabbit aortic smooth muscle cells in culture. Artery. 1980;7(6):509–518. [PubMed] [Google Scholar]
  22. Qwarnström E. E., MacFarlane S. A., Page R. C. Effects of interleukin-1 on fibroblast extracellular matrix, using a 3-dimensional culture system. J Cell Physiol. 1989 Jun;139(3):501–508. doi: 10.1002/jcp.1041390308. [DOI] [PubMed] [Google Scholar]
  23. Ratcliffe A., Tyler J. A., Hardingham T. E. Articular cartilage cultured with interleukin 1. Increased release of link protein, hyaluronate-binding region and other proteoglycan fragments. Biochem J. 1986 Sep 1;238(2):571–580. doi: 10.1042/bj2380571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rennick R. E., Campbell J. H., Campbell G. R. Vascular smooth muscle phenotype and growth behaviour can be influenced by macrophages in vitro. Atherosclerosis. 1988 May;71(1):35–43. doi: 10.1016/0021-9150(88)90300-0. [DOI] [PubMed] [Google Scholar]
  25. Robbins R. A., Wagner W. D., Sawyer L. M., Caterson B. Immunolocalization of proteoglycan types in aortas of pigeons with spontaneous or diet-induced atherosclerosis. Am J Pathol. 1989 Mar;134(3):615–626. [PMC free article] [PubMed] [Google Scholar]
  26. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ross R., Glomset J., Kariya B., Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1207–1210. doi: 10.1073/pnas.71.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rowe H. A., Wagner W. D. Arterial dermatan sulfate proteoglycan structure in pigeons susceptible to atherosclerosis. Arteriosclerosis. 1985 Jan-Feb;5(1):101–109. doi: 10.1161/01.atv.5.1.101. [DOI] [PubMed] [Google Scholar]
  29. Salisbury B. G., Wagner W. D. Isolation and preliminary characterization of proteoglycans dissociatively extracted from human aorta. J Biol Chem. 1981 Aug 10;256(15):8050–8057. [PubMed] [Google Scholar]
  30. Schmidt J. A., Mizel S. B., Cohen D., Green I. Interleukin 1, a potential regulator of fibroblast proliferation. J Immunol. 1982 May;128(5):2177–2182. [PubMed] [Google Scholar]
  31. Smith B. P., St Clair R. W., Lewis J. C. Cholesterol esterification and cholesteryl ester accumulation in cultured pigeon and monkey arterial smooth muscle cells. Exp Mol Pathol. 1979 Apr;30(2):190–208. doi: 10.1016/0014-4800(79)90053-4. [DOI] [PubMed] [Google Scholar]
  32. St Clair R. W., Randolph R. K., Jokinen M. P., Clarkson T. B., Barakat H. A. Relationship of plasma lipoproteins and the monocyte-macrophage system to atherosclerosis severity in cholesterol-fed pigeons. Arteriosclerosis. 1986 Nov-Dec;6(6):614–626. doi: 10.1161/01.atv.6.6.614. [DOI] [PubMed] [Google Scholar]
  33. Stevens R. L., Colombo M., Gonzales J. J., Hollander W., Schmid K. The glycosaminoglycans of the human artery and their changes in atherosclerosis. J Clin Invest. 1976 Aug;58(2):470–481. doi: 10.1172/JCI108491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Subbiah M. T. Prostaglandin E2 biosynthesis and effect in pigeon aorta. Possible role in atherogenesis. Atherosclerosis. 1978 Apr;29(4):487–495. doi: 10.1016/0021-9150(78)90177-6. [DOI] [PubMed] [Google Scholar]
  35. Takasu Y., Hasumi F., Mori Y. Biosynthesis of glycosaminoglycans in peritoneal macrophages from the guinea pig. Biochim Biophys Acta. 1982 Jun 16;716(3):316–323. doi: 10.1016/0304-4165(82)90022-8. [DOI] [PubMed] [Google Scholar]
  36. Tammi M., Seppälä P. O., Lehtonen A., Möttönen M. Connective tissue components in normal and atherosclerotic human coronary arteries. Atherosclerosis. 1978 Feb;29(2):191–194. doi: 10.1016/0021-9150(78)90007-2. [DOI] [PubMed] [Google Scholar]
  37. Varga J., Rosenbloom J., Jimenez S. A. Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. Biochem J. 1987 Nov 1;247(3):597–604. doi: 10.1042/bj2470597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vilcek J., Palombella V. J., Henriksen-DeStefano D., Swenson C., Feinman R., Hirai M., Tsujimoto M. Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med. 1986 Mar 1;163(3):632–643. doi: 10.1084/jem.163.3.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wagner W. D., Nohlgren S. R. Aortic glycosaminoglycans in genetically selected WC-2 pigeons with increased atherosclerosis susceptibility. Arteriosclerosis. 1981 May-Jun;1(3):192–201. doi: 10.1161/01.atv.1.3.192. [DOI] [PubMed] [Google Scholar]
  40. Wagner W. D., Rowe H. A., Connor J. R. Biochemical characteristics of dissociatively isolated aortic proteoglycans and their binding capacity to hyaluronic acid. J Biol Chem. 1983 Sep 25;258(18):11136–11142. [PubMed] [Google Scholar]
  41. Wagner W. D., Salisbury B. G. Aortic total glycosaminoglycan and dermatan sulfate changes in atherosclerotic rhesus monkeys. Lab Invest. 1978 Oct;39(4):322–328. [PubMed] [Google Scholar]
  42. Yanagishita M., Hascall V. C., Rodbard D. Biosynthesis of proteoglycans by rat granuloma cells cultured in vitro: modulation by gonadotropins, steroid hormones, prostaglandins, and a cyclic nucleotide. Endocrinology. 1981 Nov;109(5):1641–1649. doi: 10.1210/endo-109-5-1641. [DOI] [PubMed] [Google Scholar]

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