Skip to main content
Log in

Control of glucan-induced systemic granulomatosis by cyclosporine A

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

This study has shown that cyclosporine A (CyA), under certain conditions, is a powerful inhibitor of intravascular and extravascular monocyte/macrophage accumulation. Experiments were carried out in Lewis rats in which intravenous injection of particulate glucan calls forth a striking granulomatous response in lung, liver, and spleen and produces a marked stimulation of splenic erythro- and myelopoiesis. In agreement with the results of others, there was also a considerable elevation in monocyte/macrophage chemoattractant levels in the bronchoalveolar lavage fluid, which is held to be a key reaction in the pathogenesis of the histologic lesions. Treatment of the animals with subcutaneous injections of CyA prevented the rise in the chemoattractant activity and suppressed the granulomatous organ infiltration as well as the splenic hemopoiesis. The findings supply new insights into the activities of CyA and would support its clinical use in macrophage-dominated diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yokum, D. E., J. B. Allen, S. M. Wahl, G. B. Calandra, andR. L. Wilder. 1986. Inhibition by cyclosporin A of streptococcal cell wall-induced arthritis and hepatic granulomas in rats.Arthritis Rheum. 29:262–273.

    PubMed  Google Scholar 

  2. Geratz, J. D., K. B. Pryzwansky, J. H. Schwab, S. K. Anderle, andR. R. Tidwell. 1993. Suppression of local and systemic responses in streptococcal cell wall-induced acute inflammation of the air pouch by cyclosporine A. Comparison with the effects of two antiinflammatory bis-benzimidazoles.Am. J. Pathol. 142:1227–1237.

    PubMed  Google Scholar 

  3. Di Lucio, N. R. 1976. Pharmacology of the reticuloendothelial system—accent on glucan.Adv. Exp. Med. Biol. 73A:412–421.

    Google Scholar 

  4. Deimann, W., andH. D. Fahimi. 1980. Hepatic granulomas induced by glucan. An ultrastructural and peroxidase-cytochemical study.Lab. Invest. 43:172–181.

    PubMed  Google Scholar 

  5. Johnson, K. J., M. Glovsky, andD. Schrier. 1984. Pulmonary granulomatous vasculitis induced in rats by treatment with glucan.Am. J. Pathol. 114:515–516.

    PubMed  Google Scholar 

  6. Bowers, G. J., M. L. Patchen, T. J. MacVittie, E. F. Hirsch, andM. P. Fink. 1986. A comparative evaluation of particulate and soluble glucan in an endotoxin model.Int. J. Immunopharmacol. 8:313–321.

    PubMed  Google Scholar 

  7. Jones, M. L., andJ. S. Warren. 1989. Monocyte chemoattractant protein 1 in a rat model of pulmonary granulomatosis.Lab. Invest. 66:498–503.

    Google Scholar 

  8. Falk, W., R. H. Goodwin, Jr., andE. J. Leonard. 1980. A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration.J. Immunol. Methods 33:239–247.

    PubMed  Google Scholar 

  9. Fawcett, D. W. 1955. An experimental study of mast cell degranulation and regeneration.Anat. Rec. 121:29–51.

    PubMed  Google Scholar 

  10. Geratz, J. D., R. R. Tidwell, R. J. Lombardy, J. H. Schwab, S. K. Anderle, andK. B. Pryzwansky. 1991. Streptococcal cell wall-induced systemic disease. Beneficial effects oftrans-bis(5-amidino-2-benzimidazolyl)ethene, a novel, macrophage-directed antiinflammatory agent.Am. J. Pathol. 139:921–931.

    PubMed  Google Scholar 

  11. Wahl, S. M., J. B. Allen, S. Dougherty, V. Evequoz, D. H. Pluznik, R. L. Wilder, A. R. Hand, andL. M. Wahl. 1986. T. lymphocyte-dependent evolution of bacterial cell wall-induced hepatic granulomas.J. Immunol. 137:2199–2209.

    PubMed  Google Scholar 

  12. Geratz, J. D., R. R. 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.

    PubMed  Google Scholar 

  13. Niskanen, E. O., C. Burgaleta, M. J. Cline, andD. W. Golde. 1978. Effects of glucan, a macrophage activator, on murine hemopoietic cell proliferation in diffusion chambers in mice.Cancer Res. 38:1406–1409.

    PubMed  Google Scholar 

  14. Rasmussen, L. T., P. E. Lipsky, andR. Seljelid. 1987. Production of prostaglandin E2 and interleukin 1 by mouse peritoneal macrophages stimulated withβ-1,3-d-glucan derivatized plastic beads.Scand. J. Immunol. 26:731–736.

    PubMed  Google Scholar 

  15. Hoffmann, O. A., E. J. Olson, andA. H. Limper. 1993. Fungalβ-glucans modulate macrophage release of tumor necrosis factor-α in response to bacterial lipopolysaccharide.Immunol. Lett. 37:19–25.

    PubMed  Google Scholar 

  16. Bevilacqua, M. P., J. S. Pober, M. E. Wheeler, R. S. Cotran, andM. A. Gimbrone, Jr. 1985. Interleukin-1 acts on cultured human vascular endothelium to increase adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines.J. Clin. Invest. 76:2003–2011.

    PubMed  Google Scholar 

  17. Barton, P. A., M. M. Imlay, C. M. Flory, andJ. S. Warren. 1994. Role of intercellular adhesion molecule-1 (ICAM-1) in glucan-induced pulmonary granulomatosis in the rat.FASEB J. 8:A236.

    Google Scholar 

  18. Imlay, M. M., J. Shen, M. Alrawi, C. M. Flory, andJ. S. Warren. 1994. Locally produced monocyte chemoattractant protein-1 (MCP-1) mediates monocyte-endothelial adhesive and killing interactions.FASEB J. 8:A326.

    Google Scholar 

  19. Yoshimura, T., N. Yuhki, S. K. Moore, E. Apella, M. I. Lerman, andE. J. Leonard. 1989. Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE.FEBS Lett. 244:487–493.

    PubMed  Google Scholar 

  20. Rollins, B. J., T. Yoshimura, E. J. Leonard, andJ. S. Pober. 1990. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE.Am. J. Pathol. 136:1229–1233.

    PubMed  Google Scholar 

  21. Li, Y.-S., Y.-J. Shyy, J. G. Wright, A. J. Valente, J. F. Cornhill, andP. E. Kolattukudy. 1993. The expression of monocyte chemotactic protein (MCP-1) in human vascular endothelium in vitro and in vivo.Mol. Cell. Biol. 126:61–68.

    Google Scholar 

  22. Villiger, P. M., R. Terkeltaub, andM. Lotz. 1992. Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage.J. Clin. Invest. 90:488–496.

    PubMed  Google Scholar 

  23. Introna, M., R. C. Bast, Jr., C. S. Tannenbaum, T. A. Hamilton, andD. O. Adams. 1987. The effect of LPS on expression of the early “competence” genes JE and KC in murine peritoneal macrophages.J. Immunol. 138:3891–3896.

    PubMed  Google Scholar 

  24. Denholm, E. M., F. M. Wolber, andS. H. Phan. 1989. Secretion of monocyte chemotactic activity by alveolar macrophages.Am. J. Pathol. 135:571–580.

    PubMed  Google Scholar 

  25. Szturm, K., J. R. Jeffery, D. N. Rush, andR. M. McKenna. 1989. Cyclosporin A and G inhibition of cytokine production.Transplant. Proc. 21:857.

    PubMed  Google Scholar 

  26. Moutabarrik, A., S. Takahara, M. Namiki, Y. Kokado, T. Seguchi, K. Yokokawa, Y. Takano, D. Zaid, M. Ishibashi, andA. Okuyama. 1993. Effect of FK 506 and cyclosporine on the expression of IL-6 and its receptor on stimulated monocytes.Transplant. Proc. 25:2320–2321.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Geratz, J.D., Pryzwansky, K.B., Anderle, S.K. et al. Control of glucan-induced systemic granulomatosis by cyclosporine A. Inflammation 19, 221–231 (1995). https://doi.org/10.1007/BF01534463

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01534463

Keywords

Navigation