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. 1983 Aug 1;97(2):351–358. doi: 10.1083/jcb.97.2.351

Induction of chondroitin sulfate proteoglycan synthesis and secretion in lymphocytes and monocytes

PMCID: PMC2112514  PMID: 6604059

Abstract

The ability of mononuclear leukocytes to synthesize and secrete proteoglycans was evaluated. Using radiolabeling with H2 35SO4, it is shown that peripheral blood mononuclear cells (PBMC) and their major subpopulations (B cells, T cells, and monocytes), as well as mouse spleen cells, all secreted easily detectable proteoglycan. After 24-h labeling periods, 90% of macromolecular 35S could be detected in culture media. This material was primarily (greater than 95%) chondroitin-4-sulfate proteoglycan (CSPG). Production and secretion of CSPG could be stimulated more than 200% in PBMC and 300% in T cell populations by high concentrations of concanavalin A and phorbol 12- myristate-13-acetate; lipopolysaccharide induced a small (twofold) but reproducible increase in CSPG secretion by adherent mononuclear leukocytes. The CSPG secreted by PBMC was relatively small in size compared to chondrocyte CSPG (130,000 daltons vs. 2-4 million daltons) but possessed similar sizes of glycosaminoglycan chains and greater solubility in low ionic strength solutions. This sulfated polyanion, which was produced endogenously by leukocytes and was actively secreted, might function as a co-mediator or "second messenger" in certain immune responses.

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Selected References

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  1. Barber A. J., Käser-Glanzmann R., Jakábová M., Lüscher E. F. Characterization of a chondroitin 4 -sulfate proteoglycan carrier for heparin neutralizing activity (platelet factor 4 ) released from human blood platelets. Biochim Biophys Acta. 1972 Dec 29;286(2):312–329. [PubMed] [Google Scholar]
  2. Bey R. F., Johnson R. C., Fitzgerald T. J. Suppression of lymphocyte response to concanavalin A by mucopolysaccharide material from Treponema pallidum-infected rabbits. Infect Immun. 1979 Oct;26(1):64–69. doi: 10.1128/iai.26.1.64-69.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhavanandan V. P., Davidson E. A. Mucopolysaccharides associated with nuclei of cultured mammalian cells. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2032–2036. doi: 10.1073/pnas.72.6.2032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cifonelli J. A., King J. The distribution of 2-acetamido-2-deoxy-D-glucose residues in mammalian heparins. Carbohydr Res. 1972 Feb;21(2):173–186. doi: 10.1016/s0008-6215(00)82144-8. [DOI] [PubMed] [Google Scholar]
  5. Darzynkiewicz Z., Balazs E. A. Effect of connective tissue intercellular matrix on lymphocyte stimulation. Exp Cell Res. 1971 May;66(1):113–123. doi: 10.1016/s0014-4827(71)80018-6. [DOI] [PubMed] [Google Scholar]
  6. Dean M. F., Muir H. Separation of a proteoglycan fraction from Kurloff cells stimulating protein synthesis in macrophages. Biochem J. 1975 Mar;146(3):557–563. doi: 10.1042/bj1460557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dean M. F., Muir H. The characterization of a protein-polysaccharide isolated from Kurloff cells of the guinea pig. Biochem J. 1970 Aug;118(5):783–790. doi: 10.1042/bj1180783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dorfman A., Vertel B. M., Schwartz N. B. Immunological methods in the study of chondroitin sulfate proteoglycans. Curr Top Dev Biol. 1980;14(Pt 2):169–198. doi: 10.1016/s0070-2153(08)60194-5. [DOI] [PubMed] [Google Scholar]
  9. Farrar J. J., Benjamin W. R., Hilfiker M. L., Howard M., Farrar W. L., Fuller-Farrar J. The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T cell and antibody-forming B cell responses. Immunol Rev. 1982;63:129–166. doi: 10.1111/j.1600-065x.1982.tb00414.x. [DOI] [PubMed] [Google Scholar]
  10. Fransson L. A., Sjöberg I., Chiarugi V. P. Co-polymeric glycosaminoglycans in transformed cells. Transformation-dependent changes in the self-associating properties of cell-surface heparan sulfate. J Biol Chem. 1981 Dec 25;256(24):13044–13047. [PubMed] [Google Scholar]
  11. Gregory J. D. Multiple aggregation factors in cartilage proteoglycan. Biochem J. 1973 Jun;133(2):383–386. doi: 10.1042/bj1330383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gronowicz E., Coutinho A. Selective triggering of B cell subpopulations by mitogens. Eur J Immunol. 1974 Nov;4(11):771–776. doi: 10.1002/eji.1830041113. [DOI] [PubMed] [Google Scholar]
  13. Hascall V. C., Jr, Kimura J. H. Biosynthesis, secretion, and aggregation of proteoglycans by rat chondrosarcoma chondrocytes. Ala J Med Sci. 1981 Jan;18(1):29–35. [PubMed] [Google Scholar]
  14. Hascall V. C., Oegema T. R., Brown M., Caplan A. I. Isolation and characterization of proteoglycans from chick limb bud chondrocytes grown in vitro. J Biol Chem. 1976 Jun 10;251(11):3511–3519. [PubMed] [Google Scholar]
  15. Hascall V. C., Riolo R. L. Characteristics of the protein-keratan sulfate core and of keratan sulfate prepared from bovine nasal cartilage proteoglycan. J Biol Chem. 1972 Jul 25;247(14):4529–4538. [PubMed] [Google Scholar]
  16. Heinegård D., Hascall V. C. Aggregation of cartilage proteoglycans. 3. Characteristics of the proteins isolated from trypsin digests of aggregates. J Biol Chem. 1974 Jul 10;249(13):4250–4256. [PubMed] [Google Scholar]
  17. Honda A., Kanke Y., Mori Y. Proteoglycans and glycoproteins from bovine heart valve. Density-gradient ultracentrifugal and gel chromatographic behavior of the valvular matrix macromolecules under dissociative and associative conditions. J Biochem. 1977 Jun;81(6):1595–1603. doi: 10.1093/oxfordjournals.jbchem.a131618. [DOI] [PubMed] [Google Scholar]
  18. Kanwar Y. S., Hascall V. C., Farquhar M. G. Partial characterization of newly synthesized proteoglycans isolated from the glomerular basement membrane. J Cell Biol. 1981 Aug;90(2):527–532. doi: 10.1083/jcb.90.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kjellén L., Oldberg A., Hök M. Cell-surface heparan sulfate. Mechanisms of proteoglycan-cell association. J Biol Chem. 1980 Nov 10;255(21):10407–10413. [PubMed] [Google Scholar]
  20. Kumazawa Y., Mizunoe K., Otsuka Y. Immunostimulating polysaccharide separated from hot water extract of Angelica acutiloba Kitagawa (Yamato tohki). Immunology. 1982 Sep;47(1):75–83. [PMC free article] [PubMed] [Google Scholar]
  21. Levitt D., Dorfman A. Concepts and mechanisms of cartilage differentiation. Curr Top Dev Biol. 1974;8:103–149. doi: 10.1016/s0070-2153(08)60607-9. [DOI] [PubMed] [Google Scholar]
  22. Levitt D., Dorfman A. Control of chondrogenesis in limb-bud cell cultures by bromodeoxyuridine. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2201–2205. doi: 10.1073/pnas.70.8.2201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levitt D., Dorfman A. The irreversible inhibition of differentiation of limb-bud mesenchyme by bromodeoxyuridine. Proc Natl Acad Sci U S A. 1972 May;69(5):1253–1257. doi: 10.1073/pnas.69.5.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Levitt D., Griffin N. B., Egan M. L. Mitogen-induced plasma cell differentiation in patients with multiple sclerosis. J Immunol. 1980 May;124(5):2117–2121. [PubMed] [Google Scholar]
  25. Lowther D. A., Preston B. N., Meyer F. A. Isolation and properties of chondroitin sulphates from bovine heart valves. Biochem J. 1970 Jul;118(4):595–601. doi: 10.1042/bj1180595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Margolis R. U., Lalley K., Kiang W. L., Crockett C., Margolis R. K. Isolation and properties of a soluble chondroitin sulfate proteoglycan from brain. Biochem Biophys Res Commun. 1976 Dec 20;73(4):1018–1024. doi: 10.1016/0006-291x(76)90224-2. [DOI] [PubMed] [Google Scholar]
  27. Mutoh S., Funakoshi I., Ui N., Yamashina I. Structural characterization of proteoheparan sulfate isolated from plasma membranes of an ascites hepatoma, AH 66. Arch Biochem Biophys. 1980 Jun;202(1):137–143. doi: 10.1016/0003-9861(80)90415-4. [DOI] [PubMed] [Google Scholar]
  28. Norling B., Glimelius B., Westermark B., Wasteson A. A chondroitin sulphate proteoglycan from human cultured glial cells aggregates with hyaluronic acid. Biochem Biophys Res Commun. 1978 Oct 30;84(4):914–921. doi: 10.1016/0006-291x(78)91670-4. [DOI] [PubMed] [Google Scholar]
  29. Nozoe M., Dennis M. V., Herman J. H. Modulation of human lymphocyte response by cartilage proteoglycans and glycosaminoglycans--a comparison between normal subjects and patients with rheumatoid arthritis. Clin Immunol Immunopathol. 1979 Apr;12(4):369–381. doi: 10.1016/0090-1229(79)90042-4. [DOI] [PubMed] [Google Scholar]
  30. Okayama M., Kimata K., Suzuki S. The influence of p-nitrophenyl beta-d-xyloside on the synthesis of proteochondroitin sulfate by slices of embryonic chick cartilage. J Biochem. 1973 Nov;74(5):1069–1073. [PubMed] [Google Scholar]
  31. Oldberg A., Kjellén L., Hök M. Cell-surface heparan sulfate. Isolation and characterization of a proteoglycan from rat liver membranes. J Biol Chem. 1979 Sep 10;254(17):8505–8510. [PubMed] [Google Scholar]
  32. Olsson I., Gardell S. Biosynthesis of glycosaminoglycans in leukocytes. Biochim Biophys Acta. 1971 May 18;237(2):203–213. doi: 10.1016/0304-4165(71)90312-6. [DOI] [PubMed] [Google Scholar]
  33. Olsson I., Gardell S. Isolation and characterization of glycosaminoglycans from human leukocytes and platelets. Biochim Biophys Acta. 1967 Jul 25;141(2):348–357. doi: 10.1016/0304-4165(67)90109-2. [DOI] [PubMed] [Google Scholar]
  34. Olsson I. Mucopolysaccharides of rabbit bone marrow cells. Identification and properties. Exp Cell Res. 1971 Aug;67(2):416–426. doi: 10.1016/0014-4827(71)90427-7. [DOI] [PubMed] [Google Scholar]
  35. Pellegrino M. A., Ferrone S., Dierich M. P., Reisfeld R. A. Enhancement of sheep red blood cell human lymphocyte rosette formation by the sulfhydryl compound 2-amino ethylisothiouronium bromide. Clin Immunol Immunopathol. 1975 Jan;3(3):324–333. doi: 10.1016/0090-1229(75)90019-7. [DOI] [PubMed] [Google Scholar]
  36. Poole A. R., Pidoux I., Reiner A., Cöster L., Hassell J. R. Mammalian eyes and associated tissues contain molecules that are immunologically related to cartilage proteoglycan and link protein. J Cell Biol. 1982 Jun;93(3):910–920. doi: 10.1083/jcb.93.3.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Reinherz E. L., Rubinstein A., Geha R. S., Strelkauskas A. J., Rosen F. S., Schlossman S. F. Abnormalities of immunoregulatory T cells in disorders of immune function. N Engl J Med. 1979 Nov 8;301(19):1018–1022. doi: 10.1056/NEJM197911083011902. [DOI] [PubMed] [Google Scholar]
  38. Saito H., Yamagata T., Suzuki S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J Biol Chem. 1968 Apr 10;243(7):1536–1542. [PubMed] [Google Scholar]
  39. Schwartz N. B., Galligani L., Ho P. L., Dorfman A. Stimulation of synthesis of free chondroitin sulfate chains by beta-D-xylosides in cultured cells. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4047–4051. doi: 10.1073/pnas.71.10.4047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schwartz N. B., Ho P. L., Dorfman A. Effect of beta-xylosides on synthesis of cartilage-specific proteoglycan in chondrocyte cultures. Biochem Biophys Res Commun. 1976 Aug 9;71(3):851–856. doi: 10.1016/0006-291x(76)90909-8. [DOI] [PubMed] [Google Scholar]
  41. Schwartz N. B. Regulation of chondroitin sulfate synthesis. Effect of beta-xylosides on synthesis of chondroitin sulfate proteoglycan, chondroitin sulfate chains, and core protein. J Biol Chem. 1977 Sep 25;252(18):6316–6321. [PubMed] [Google Scholar]
  42. Shively J. E., Conrad H. E. Formation of anhydrosugars in the chemical depolymerization of heparin. Biochemistry. 1976 Sep 7;15(18):3932–3942. doi: 10.1021/bi00663a005. [DOI] [PubMed] [Google Scholar]
  43. Silvestri L., Baker J. R., Rodén L., Stroud R. M. The C1q inhibitor in serum is a chondroitin 4-sulfate proteoglycan. J Biol Chem. 1981 Jul 25;256(14):7383–7387. [PubMed] [Google Scholar]
  44. Smith G. N., Jr, Newsome D. A. The nature and origin of the glycosaminoglycans of the embryonic chick vitreous body. Dev Biol. 1978 Jan;62(1):65–77. doi: 10.1016/0012-1606(78)90093-3. [DOI] [PubMed] [Google Scholar]
  45. Spooncer E., Gallagher J. T., Krizsa F., Dexter T. M. Regulation of haemopoiesis in long-term bone marrow cultures. IV. Glycosaminoglycan synthesis and the stimulation of haemopoiesis by beta-D-xylosides. J Cell Biol. 1983 Feb;96(2):510–514. doi: 10.1083/jcb.96.2.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sugahara K., Ho P. L., Dorfman A. Chemical and immunological characterization of proteoglycans of embryonic chick calvaria. Dev Biol. 1981 Jul 15;85(1):180–189. doi: 10.1016/0012-1606(81)90248-7. [DOI] [PubMed] [Google Scholar]
  47. Toole B. P., Okayama M., Orkin R. W., Yoshimura M., Muto M., Kaji A. Developmental roles of hyaluronate and chondroitin sulfate proteoglycans. Soc Gen Physiol Ser. 1977;32:139–154. [PubMed] [Google Scholar]
  48. Upholt W. B., Vertel B. M., Dorfman A. Cell-free translation of cartilage RNAs. Ala J Med Sci. 1981 Jan;18(1):35–40. [PubMed] [Google Scholar]
  49. Wasteson A. A method for the determination of the molecular weight and molecular-weight distribution of chondroitin sulphate. J Chromatogr. 1971 Jul 8;59(1):87–97. doi: 10.1016/s0021-9673(01)80009-1. [DOI] [PubMed] [Google Scholar]
  50. Yanagishita M., Hascall V. C. Biosynthesis of proteoglycans by rat granulosa cells cultured in vitro. J Biol Chem. 1979 Dec 25;254(24):12355–12364. [PubMed] [Google Scholar]

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