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Nitric Oxide Modulates MCP-1 Expression in Endothelial Cells: Implications for the Pathogenesis of Pulmonary Granulomatous Vasculitis

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Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a pivotal mediator of angiocentric granuloma formation in glucan-induced pulmonary granulomatous vasculitis. Based on the rationale that mononuclear phagocytes retrieved from granulomas are rich sources of nitric oxide (NO) and that the recruitment of mononuclear phagocytes into lesions abates as granuloma formation slows, we tested the hypothesis that MCP-1 gene expression is regulated by a NO-sensitive mechanism. Preexposure of endothelial cell (EC) monolayers to NO donor compounds markedly reduced cytokine-induced MCP-1 expression and cytosolic-to-nuclear translocation of nuclear factor-kappa B (NF-κB), reversed fluctuations in endothelial reduced glutathione (GSH) pools but did not affect cGMP concentrations. The lungs of mice bearing targeted disruptions of the inducible nitric oxide synthase (iNOS) gene exhibited significantly higher concentrations of MCP-1 following glucan infusion than did those of wild-type mice. Cumulatively, these data suggest that NO suppresses MCP-1 expression by blunting the redox changes associated with cytokine-induced EC activation.

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References

  1. Robinson, D. S., L. Richeldi, C. Saltini, and R. M. Du Bois. 1997. Granulamatous processes. In: The Lung: Scientific Foundations, 2nd edn., R. G. Crystal, J. B. West, E.R. Weibel, and P. J. Barnes, eds., Lippincott-Raven, Philadelphia, pp. 2395–2409.

    Google Scholar 

  2. Strieter, R. M. and S. L. Kunkel. 1997. Chemokines. In: The lung: Scientific foundations, 2nd edn., R. G. Crystal, J. B. West, E.R. Weibel, and P. J. Barnes, eds. Lippincott-Raven, Philadelphia, pp. 155–186.

    Google Scholar 

  3. Rollins, B. R., T. Yoshimura, E. L. Leonard, and J. S. Pober. 1990. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am. J. Pathol. 136(6):1229–1233.

    Google Scholar 

  4. Flory, C. M., M. L. Jones, and J. S. Warren. 1993. Pulmonary granuloma formation in the rat is partially dependent on monocyte chemoattractant protein–1. Lab. Invest. 69(4):396–404.

    Google Scholar 

  5. Flory, C. M, M. L. Jones, B. F. Miller, and J. S. Warren. 1995. Regulatory roles of tumor necrosis factor-α and interleukin-1β in monocyte chemoattractant protein-1-mediated pulmonary granuloma formation in the rat. Am. J. Pathol. 146:450–462.

    Google Scholar 

  6. Jones, M. L. and J. S. Warren. 1992. Monocyte chemoattractant protein 1 in a rat model of pulmonary granulomatosis. Lab. Invest. 66(4):498–503.

    Google Scholar 

  7. Kilgore, K. S., M. M Imlay, J. P. Szaflarski, F. S. Silverstein, A. Malani, V. M. Evans, and J. S. Warren. 1997. Neutrophils and reactive oxygen intermediates mediate glucan-induced pulmonary granuloma formation through the local induction of monocyte chemoattractant protein-1. Lab. Invest. 76(2):191–201.

    Google Scholar 

  8. Kilgore, K. S., K. L. Powers, M. M. Imlay, A. Malani, D. I. Allen, J. T. Beyer, M. B. Anderson, and J. S. Warren. 1998. The carbohydrate sialyl Lewis(x) (sLe(x)) sulfated glycomimetic GM2941 attenuates glucan-induced pulmonary granulomatous vasculitis in the rat. J. Pharmacol. Exp. Ther. 286(1):439–446.

    Google Scholar 

  9. Desai, A., X. Huang, and J. S. Warren. 1999. Intracellular glutathione redox status modulates MCP-1 expression in pulmonary granulomatous vasculitis. Lab. Invest. 79(7):837–847.

    Google Scholar 

  10. Wynyard, P. G. and D. R. Blake. 1997. Antioxidants, redox-regulated transcription factors, and inflammation. Adv. Pharmacol. 38:403–421.

    Google Scholar 

  11. Desai, A., M. J. Miller, H. F. Gomez, and J. S. Warren. 1999. Loxosceles deserta spider venom induces NF-κB-dependent chemokine production by endothelial cells. Clin. Toxical. 37(4):447–456.

    Google Scholar 

  12. Hrabie, J. A., J. R. Klose, and D. A. Wink. 1993. New nitric-oxide releasing zwitterions derived from polyamines. J. Org. Chem. 58:1472–1476.

    Google Scholar 

  13. Desai, A., H. A. Lankford, and J. S. Warren. 2001. Homocysteine augments cytokine-induced chemokine expression in human vascular smooth muscle cells: Implications for atherogenesis. Inflammation 25(3):179–186.

    Google Scholar 

  14. Smith, P. K., R. I. Krohn, G. T. Hermanso, A. K. Mallia, A. K. Gartner, E. K. Provenzano, E. K. Fujimoto, N. M. Goeke, B. J. Olson, and D. C. Klenk. 1985. Measurement of protein using bicinchoninic acid. Anal. Biochem. 150:76–85.

    Google Scholar 

  15. Linton, M. and P. S. Gallo Jr. 1975. The Practical Statistician: Simplified Handbook of Statistics. Brooks/Cole, Monterey, CA.

    Google Scholar 

  16. Martin, T., P. M. Cardarelli, G. C. N. Parry, K. A. Felts, and R. R. Cobb. 1997. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-κB and AP-1. Eur. J. Immunol. 27(5):1091–1097.

    Google Scholar 

  17. Murad, F. 1994. Regulation of cytosolic guanylyl cyclase by nitric oxide: the NO-cyclic GMP signal transduction system. Adv. Pharmacol. 26:19–33.

    Google Scholar 

  18. Zeiher, A. M., B. Fisslthaler, B. Schray-Utz, and R. Busse. 1995. Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. Circ. Res. 76:980–986.

    Google Scholar 

  19. Tsao, P. S., B. Wang, R. Buitrago, J. Y. Shyy, and J. P. Cooke. 1997. Nitric oxide regulates monocyte chemotactic protein-1. Circulation 96:934–940.

    Google Scholar 

  20. Khan, B. V., D. G. Harrison, M. T. Olbrych, R. W. Alexander, and R. M. Medford. 1996. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc. Natl. Acad. Sci. 93(17):9114–9119.

    Google Scholar 

  21. Katsuyama, K., M. Shichiri, F. Marumo, and Y. Hirata. 1998. NO inhibits cytokine-induced iNOS expression and NF-κB activaton by interfering with phosphorylation and degradation of IκB-α. Arterioscler. Thromb. Vasc. Biol. 18:1796–1802.

    Google Scholar 

  22. Peng, H., P. Libbey, and J. K. Liao. 1995. Induction and stabilization of IκB-α by nitric oxide mediates inhibition of NF-κB. J. Biol. Chem. 270(23):14214–14219.

    Google Scholar 

  23. Janssen-Heininger, Y. M., N. E. Poynter, and P. A. Baeuerle. 2000. Recent advances towards understanding redox-mechanisms in the activation of nuclear factor κB. Free Radic. Biol. Med. 28(9):1317–1327.

    Google Scholar 

  24. Umansky, V., S. P. Hehner, A. Dumont, T. G. Hofmann, V. Schirrmacher, W. Droge, and M. Lienhard Schmitz. 1998. Co-stimulatory effect of nitric oxide on endothelial NF-κB implies a physiological self-amplifying mechanism. Eur. J. Immunol. 28:2276–2282.

    Google Scholar 

  25. Xie, Q. W., Y. Kashiwabara, and C. Nathan. 1994. Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J. Biol. Chem. 269(7):4705–4708.

    Google Scholar 

  26. Niu, X. F., C. W. Smith, and P. Kubes. 1994. Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils. Circ. Res. 74(6):1133–1140.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan

    Anjali Desai, Mark J. Miller, Xiaodong Huang & Jeffrey S. Warren

Authors
  1. Anjali Desai
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  2. Mark J. Miller
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  3. Xiaodong Huang
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  4. Jeffrey S. Warren
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Correspondence to Jeffrey S. Warren.

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Desai, A., Miller, M.J., Huang, X. et al. Nitric Oxide Modulates MCP-1 Expression in Endothelial Cells: Implications for the Pathogenesis of Pulmonary Granulomatous Vasculitis. Inflammation 27, 213–223 (2003). https://doi.org/10.1023/A:1025036530605

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