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Bone-resorbing activity is expressed by rat macrophages in response to arthropathic streptococcal cell wall polymers


Rat peritoneal macrophages stimulated in vivo by group A streptococcal peptidoglycan-polysaccharide (PG-APS) resorb bone as measured by solubilization of45Ca from radiolabeled, devitalized bone chips. Activity was strain-dependent and correlated with the susceptibility of rat strains to PG-APS-induced arthritis. PG-APS-stimulated macrophages from the resistant Buf rat strain were not induced to resorb bone, but ingested equivalent concentrations of PG-APS compared to bone-resorbing macrophages from the arthritis-susceptible Lew strain. Resorptive activity peaked at three to five days and decreased to background levels by 10 days after injection. PG-APS-stimulated macrophages from congenitally athymic Lew rats were as effective as macrophages from heterozygous littermates at resorbing bone. Lew macrophages were also responsive to small, nonarthropathic PG-APS polymers generated by mutanolysin digestion. Resident peritoneal macrophages did not respond to stimulation by PG-APS in vitro. Indomethacin at a concentration of 10 μg/ml was an effective blockade against PG-APS-induced macrophage bone resorption in vitro, but catalase was ineffective. These results indicate that expression of rat macrophage bone-resorbing activity reflects genetic regulation of the response to PG-APS rather than a defect in ingestion of these polymers and imply that PG-APS-stimulated, bone-resorbing macrophages may contribute to early, initial bone destruction that occurs in inflammatory arthritis.

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  1. 1.

    Cromartie, W. J., J. G. Craddock, J. H. Schwab, S. K. Anderle, andC. H. Yang. 1977. Arthritis in rats after systemic injection of streptococcal cells and cell walls.J. Exp. Med. 146:1585–1602.

  2. 2.

    Dalldorf, F. G., W. J. Cromartie, S. K. Anderle, R. L. Clark, andJ. H. Schwab. 1980. The relation of experimental arthritis to the distribution of streptococcal cell wall fragments.Am. J. Path. 100:383–402.

  3. 3.

    Wilder, R. L., G. B. Calandra, A. J. Garvin, K. D. Wright, andC. T. Hansen. 1982. Strain and sex variation in the susceptibility to streptococcal cell wall-induced polyarthritis in the rat.Arthritis Rheum. 25:1064–1072.

  4. 4.

    Schwab, J. H., W. J. Cromartie, S. H. Ohanian, andJ. G. Craddock. 1967. Association of experimental chronic arthritis with the persistence of group A streptococcal cell walls in the articular tissue.J. Bacteriol. 94:1728–1735.

  5. 5.

    Spitznagel, J. K., K. J. Goodrum, andD. J. Warejcka. 1983. Rat arthritis due to whole group B streptococci. Clinical and histopathologic features compared with group A and D.Am. J. Pathol. 112:37–47.

  6. 6.

    Anderle, S. K., J. J. Greenblatt, W. J. Cromartie, R. Clark, andJ. H. Schwab. 1979. Modulation of the susceptibility of inbred and outbred rats to arthritis induced by cell walls from group A streptococci.Infect. Immun. 25:484–490.

  7. 7.

    Bertolini, D. R., G. T. Nedwin, T. Bringman, D. Smith, andG. R. Mundy. 1986. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors.Nature 319:516–518.

  8. 8.

    Dominguez, J. H., andG. R. Mundy. 1980. Monocytes mediate osteoclastic bone resorption by prostaglandin production.Calcif. Tiss. Int. 31:29–34.

  9. 9.

    Lorenzo, J. A., S. L. Sousa, andM. Centrella. 1988. Interleukin-1 in combination with transforming growth factor-alpha produces enhanced bone resorption in vitro.Endocrinology 123:2194–2200.

  10. 10.

    Mizel, S. B., J. M. Dayer, S. M. Frane, andS. E. Mergenhagen. 1981. Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1).Proc. Natl. Acad. Sci. U.S.A. 78:2474–2477.

  11. 11.

    Mundy, G. R., A. J. Altman, M. D. Gondek, andJ. G. Bandelin. 1977. Direct resorption of bone by human monocytes.Science 6:1109–1111.

  12. 12.

    Wahl, L. M., S. M. Wahl, S. E. Mergenhagen, andG. R. Martin. 1974. Collagenase production by endotoxin-activated macrophages.Proc. Natl. Acad. Sci. U.S.A. 71:3598–3601.

  13. 13.

    Walker, D. G. 1975. Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells.Science 0:784–785.

  14. 14.

    McArthur, W., A. M. Yaari, andI. M. Shapiro. 1980. Bone solubilization by mononuclear cells.Lab. Invest. 42:450–456.

  15. 15.

    Chetty, C., D. G. Klapper, andJ. H. Schwab. 1982. Soluble peptidoglycan-polysaccharide fragments of the bacterial cell wall induce acute inflammation.Infect. Immun. 38:1010–1119.

  16. 16.

    Fox, A., R. R. Brown, S. K. Anderle, C. Chetty, W. J. Cromartie, H. Gooder, andJ. H. Schwab. 1982. Arthropathic properties related to the molecular weight of peptidoglycan-polysaccharide polymers of streptococcal cell walls.Infect. Immun. 35:1003–1010.

  17. 17.

    Stimpson, S. A., R. A. Lerch, D. R. Cleland, D. P. Yarnell, R. L. Clark, W. J. Cromartie, andJ. H. Schwab. 1987. Effect of acetylation on arthropathic activity of group A streptococcal peptidoglycan-polysaccharide fragments.Infect. Immun. 55:16–23.

  18. 18.

    Yokogawa, K., S. Kawata, S. Nishimura, Y. Ikeda, andY. Yoshimura. 1974. Mutanolysin, bacteriolytic agent for cariogenic streptococci: Partial purification and properties.Antimicrob. Agents. Chemother. 6:156–165.

  19. 19.

    Janusz, M. J., C. Chetty, R. A. Eisenberg, W. J. Cromartie, andJ. H. Schwab. 1984. Treatment of experimental erosive arthritis in rats by injection of the muralytic enzyme mutanolysin.J. Exp. Med. 160:1360–1374.

  20. 20.

    Janusz, M. J., R. A. Eisenberg, andJ. H. Schwab. 1987. Effect of muralytic enzyme degradation of streptococcal cell wall on complement activation in vivo and in vitro.Inflammation 11:73–85.

  21. 21.

    Janusz, M. J., R. E. Esser, andJ. H. Schwab. 1986. In vivo degradation of bacterial cell wall by the muralytic enzyme mutanolysin.Infect. Immun. 52:459–467.

  22. 22.

    Teitelbaum, S. L., C. C. Stewart, andA. J. Kahn. 1979. Rodent peritoneal macrophages as bone resorbing cells.Calcif. Tiss. Int. 27:255–261.

  23. 23.

    Stimpson, S. A., R. R. Brown, S. K. Anderle, D. G. Klapper, R. L. Clark, W. J. Cromartie, andJ. H. Schwab. 1986. Arthropathic properties of cell wall polymers from normal flora bacteria.Infect. Immun. 51:240–249.

  24. 24.

    Dische, Z., andL. B. Shettles. 1948. A specific color reaction of methyl pentose and a spectrophotometric micromethod for their determination.J. Biol. Chem. 175:595–603.

  25. 25.

    Sokol, R. R. andF. J. Rohlf. 1969. Biometry. The Principles and Practice of Statistics in Biological Research. W. H. Freeman, San Francisco. 238.

  26. 26.

    Allan, J. B., D. G. Malone, S. M. Wahl, G. B. Calandra, andR. L. Wilder. 1985. Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation.J. Clin. Invest. 76:1042.

  27. 27.

    DeJoy, S. Q., K. M. Ferguson, T. M. Sapp, J. B. Zabriskie, A. L. Oronsky, andS. S. Kerwar. 1989. Streptococcal cell wall arthritis. Passive transfer of disease with a T cell line and crossreactivity of streptococcal cell wall antigens withMycobacterium tuberculosis.J. Exp. Med. 170:369.

  28. 28.

    Yoshino, S., L. G. Cleland, G. Mayrhoefer, R. R. Brown, andJ. H. Schwab. 1991. Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha, beta.J. Immunol. 146:4187.

  29. 29.

    Smialowicz, R. J., andJ. H. Schwab. 1977. Cytotoxicity of rat macrophages activated by persistent or biodegradable bacterial cell walls.Infect. Immun. 17:599–606.

  30. 30.

    Geratz, J. D., R. P. Tidwell, J. H. Schwab, S. K. Anderle, andK. B. Pryzwansky. 1990. Sequential events in the pathogenesis of streptococcal cell wall-induced arthritis and their modulation by bis(5-amidino-2-benzimidazolyl)methane (BABIM).Am. J. Pathol. 136:909–921.

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Bristol-Rothstein, L.A., Schwab, J.H. Bone-resorbing activity is expressed by rat macrophages in response to arthropathic streptococcal cell wall polymers. Inflammation 16, 485–496 (1992).

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  • Catalase
  • Indomethacin
  • Peritoneal Macrophage
  • Inflammatory Arthritis
  • Bone Destruction