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Inducible nitric oxide synthase in inflammation

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Summary

Inflammation, the reaction of vascularized tissue to local injury, not only limits the effects of injury; it may also be the underlying pathological process which initiates or sustains disease. In this paper, the evidence is reviewed for a role for nitric oxide (NO) as a chemical indicator of inflammation and inflammatory diseases.

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References

  • Albina, J. E., Abate, J. A. & Henry, W. L. (1991) Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. J. Immunol. 147, 144–8.

    Google Scholar 

  • Bandaletova, T., Brouet, I., Bartsch, H., Sugimura, T., Esumi, H. & Ohshima, H. (1993) Immunohistochemical localization of an inducible form of nitric oxide synthase in various organs of rats treated with Propionibacterium acnes and lipopolysaccharide. APMIS 101, 330–6.

    Google Scholar 

  • Belenky, S. N., Robbins, R. A., Rennard, S. I., Gossman, G. L., Nelson, K. J. & Rubinstein, I. (1993a) Inhibitors of nitric oxide synthase attenuate human neutrophil chemotaxis in vitro. J. Lab. Clin. Med 122, 388–94.

    Google Scholar 

  • Belenky, S. N., Robbins, R. A. & Rubinstein, I. (1993b) Nitric oxide synthase inhibitors attenuate human monocyte chemotaxis in vitro. J. Leuko. Biol. 53, 498–503.

    Google Scholar 

  • Boughton-Smith, N. K., Evans, S. M., Hawkey, C. J., Cole, A. T., Balsitis, M., Whittle, B. J. R. & Moncada, S. (1993) Nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Lancet 342, 338–40.

    Google Scholar 

  • Cattell, V. & Cook, H. T. (1993) Nitric oxide: role in the physiology and pathology of the glomerulus. Exp. Nephrol. 1, 265–80.

    Google Scholar 

  • Cattell, V., Cook, T. & Moncada, S. (1990) Glomeruli synthesize nitrite in experimental nephrotoxic nephritis. Kid. Int. 38, 1056–60.

    Google Scholar 

  • Charles, I. G., Palmer, R. M. J., Hickery, M. S., Bayliss, M. T., Chubb, A. P., Hall, V. S., Moss, D. W. & Moncada, S. (1993) Cloning, characterization and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc. Natl Acad. Sci. USA 90, 11 419–23.

    Google Scholar 

  • Cook, H. T., Ebrahim, H., Jansen, A. S., Foster, G. R., Largen, P. & Cattell, V. (1994a) Expression of the gene for inducible nitric oxide synthase in experimental glomerulonephritis in the rat. Clin. Exp. Immunol 97, 315–20.

    Google Scholar 

  • Cook, H. T., Bune, A. J., Jansen, A. S., Taylor, G. M., Loi, R. K. & Cattell, V. (1994b) Cellular localisation of inducible nitric oxide synthase in experimental endotoxic shock in the rat. Clin. Sci. 87, 179–86.

    Google Scholar 

  • DiRosa, M., Moncada, S. & Ialenti, A. (1993) Modulation of acute and chronic inflammation by endogenous nitric oxide. In Nitric Oxide: Brain and Immune System (edited by Moncada, S. et al.), pp. 231–6. London: Portland Press Proceedings.

    Google Scholar 

  • Evans, T. G., Thai, L., Granger, D. L. & Hibbs, J. B. (1993) Effect of in vivo inhibition of nitric oxide production in murine leishmaniasis. J. Immunol. 151, 907–15.

    Google Scholar 

  • Farrell, A. J., Blake, D. R., Palmer, R. M. & Moncada, S. (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann. Rheum. Dis. 51, 1219–22.

    Google Scholar 

  • Garside, P., Hutton, A. K., Severn, A., Liew, F. Y. & Mowat, A. M. (1992) Nitric oxide mediates intestinal pathology in graft-vs-host disease. Eur. J. Immunol. 22, 2141–5.

    Google Scholar 

  • Geller, D. A., Lowenstein, C. J., Shapiro, R. A., Nussler, A. K., DiSilvio, M., Wang, S. C., Nakayama, D. K., Simmons, R. L., Snyder, S. H. & Billiar, T. R. (1993) Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc. Natl Acad. Sci. USA 90, 3491–5.

    Google Scholar 

  • Green, S. J. & Nacy, C. A. (1993) Antimicrobial and immunopathologic effects of cytokine-induced nitric oxide synthesis. Curr. Opin. Inf. Dis. 6, 384–96.

    Google Scholar 

  • Hamid, Q., Springall, D. R., Riveros-Moreno, V., Chanez, P., Howarth, P., Redington, A., Bousquet, J., Godard, P., Holgate, S. & Polak, J. M. (1993) Induction of nitric oxide synthase in asthma. Lancet 342, 1510–3.

    Google Scholar 

  • Harbrecht, B. G., Billiar, T. R., Stadler, J., Demetris, A. J., Ochoa, J., Curran, R. D. & Simmons, R. L. (1992) Inhibition of nitric oxide synthesis during endotoxemia promotes intrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J. Leukoc. Biol. 52, 390–4.

    Google Scholar 

  • Hibbs, J. B., Westenfelder, C., Taintor, R., Vavrin, Z., Kablitz, C., Baranowski, R. L., Ward, J. H., Menlove, R. L., Mcmurry, M. P., Kushner, J. P. & Samlowski, W. E. (1992) Evidence for cytokine inducible nitric oxide synthesis from {spl-arginine in patients receiving interleukin-2 therapy}. Clin. Invest. 89, 867–77.

    Google Scholar 

  • Hoffman, R. A., Langrehr, J. M., Billiar, T. R., Curran, R. D. & Simmons, R. L. (1990) Alloantigen-induced activation of rat splenocytes is regulated by the oxidative metabolism of {spl-arginine}. J. Immunol. 145, 2220–6.

    Google Scholar 

  • Ialenti, A., Ianaro, A., Moncada, S. & DiRosa, M. (1992) Modulation of acute inflammation by endogenous nitric oxide. Eur. J. Pharm. 211, 177–82.

    Google Scholar 

  • Ialenti, A., Moncada, S. & DiRosa, M. (1993) Modulation of adjuvant arthritis by endogenous nitric oxide. Br. J. Pharmacol. 110, 701–6.

    Google Scholar 

  • Jansen, A., Cook, T., Taylor, G. M., Largen, P., Riveros-Moreno, V., Moncada, S. & Cattell, V. (1994) Induction of nitric oxide synthase in rat immune complex glomerulonephritis. Kidney Int. 45, 1215–9.

    Google Scholar 

  • Kaplan, S. S., Billiar, T., Curran, R. D., Zdziarski, U. E., Simmons, R. L. & Basford, R. E. (1989) Blood 74, 1885–7.

    Google Scholar 

  • Ketteler, M., Narita, I., Border, W. A. & Noble, N. A. (1993) Nitric oxide-inhibition prevents mesangial cell lysis in experimental glomerulonephritis. J. Am. Soc. Nephrol. 4, 610.

    Google Scholar 

  • Kilbourn, R. G. & Griffith, O. W. (1992) Overproduction of nitric oxide in cytokine-mediated and septic shock. J. Natl Can. Inst. 84, 827–31.

    Google Scholar 

  • Kilbourn, R. G., Jubran, A., GrossS. S., Griffith, O. W., Levi, R., Adams, J. & Lodato, R. F. (1990) Reversal of endotoxin mediated shock by NG-methyl-l-arginine, an inhibitor of nitric oxide synthesis. Biochem. Biophys. Res. Commun. 172, 1132–8.

    Google Scholar 

  • Kirk, S. J., Regan, M. C. & Barbul, A. (1990) Cloned murine T lymphocytes synthesize a molecule with the biological characteristics of nitric oxide. Biochem. Biophys. Res. Comm. 173, 660–5.

    Google Scholar 

  • Koprowski, H., Mu Zheng, Y., Heber-Katz, E., Fraser, N., Rorke, L., Fang Fu, Z., Hanlonc & Dietzschold, B. (1993) In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases. Proc. Natl Acad. Sci. USA 90, 3024–7.

    Google Scholar 

  • Kubes, P., Suzuki, M. & Granger, D. N. (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc. Natl Acad. Sci. USA 88, 4651–5.

    Google Scholar 

  • Langrehr, J. M., Hoffman, R. A., Lancaster, J. R. & Simmons, R. L. (1993) Nitric oxide — a new endogenous immunomodulator. Transplantation 55, 1205–12.

    Google Scholar 

  • Mccartney-Francis, N., Allen, J. B., Mizel, D. E., Albina, J. E., Xie, Q-W., Nathan, C. F. & Wahl, S. M. (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J. Exp. Med. 178, 749–54.

    Google Scholar 

  • Macmicking, J. D., Willenborg, D. O., Weidemann, M. J., Rockett, K. A. & Cowden, W. B. (1992) Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells. J. Exp. Med. 176, 303–7.

    Google Scholar 

  • Mcnamara, D. B., Bedi, B., Aurora, H., Tena, L., Ignarro, L. J., Kadowitz, P. J. & Akers, D. L. (1993) l-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem. Biophys. Res. Comm. 193, 291–6.

    Google Scholar 

  • Miller, M. J. S., Sadowska-Krowicka, H., Chotinaruemol, S., Kakkis, J. L. & ClarkD. A. (1993) Amelioration of chronic ileitis by nitric oxide synthase inhibition. J. Pharmacol. 264, 11–6.

    Google Scholar 

  • Mills, C. D. (1991) Molecular basis of ‘suppressor’ macrophages; arginine metabolism via the nitric oxide synthetase pathway. J. Immunol. 146, 2719–23.

    Google Scholar 

  • Mulligan, M. S., Hevel, J. M., Marletta, M. A. & Ward, P. A. (1991) Tissue injury caused by deposition of immune complexes is l-arginine dependent. Proc. Natl Acad. Sci. USA 88, 6338–42.

    Google Scholar 

  • Mulligan, M. S., Warren, J. S., Smith, C. W., Anderson, D. C., Grace, C., Rudolph, A. R. & Ward, P. A. (1992) Lung injury after deposition of IgA immune complexes. J. Immunol. 148, 3086–92.

    Google Scholar 

  • Nathan, C. (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J. 6, 3051–64.

    Google Scholar 

  • Nicholson, A. G., Haites, N. E., Mckay, N. G., Wilson, H. M., Macleod, A. M. & Benjamin, N. (1993) Induction of nitric oxide synthase in human mesangial cells. Biochem. Biophys. Res. Comm. 193, 1269–74.

    Google Scholar 

  • Nussler, A. K., Renia, L., Pasquetto, V., Miltgen, F., Matile, H. & Mazier, D. (1993) In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants. Eur. J. Immunol. 23, 882–7.

    Google Scholar 

  • Ohshima, H., Brouet, I. M., Bandaletova, T., Adachi, H., Oguchi, S., Lida, S., Kurashima, Y., Morishita, Y., Sugimura, T. & Esumi, H. (1992) Polyclonal antibody against an inducible form of nitric oxide synthase purified from the liver of rats treated with Propionibacterium acnes and lipopolysaccharide. Biochem. Biophys. Res. Commun. 187, 1291–7.

    Google Scholar 

  • Petros, A., Bennett, D. & Vallance, P. (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338, 1557–8.

    Google Scholar 

  • Pipili-Synetos, E., Sakkoula, E. & Maragoudakis, M. E. (1993) Nitric oxide is involved in the regulation of angiogenesis. Br. J. Pharmacol. 108, 855–7.

    Google Scholar 

  • Schultz, P. J. & Raij, L. (1992) Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis. J. Clin. Invest. 90, 1718–25.

    Google Scholar 

  • Sherman, P. A., Laubach, V. E., Reep, B. R. & Wood, E. R. (1993) Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumour cell line. Biochemistry 32, 11 600–5.

    Google Scholar 

  • Shi, Y., Li, H., Shen, C., Wang, J., Qin, S., Liu, R. & Pan, J. (1993) Plasma nitric oxide levels in newborn infants with sepsis. J. Pediatr. 123, 435–8.

    Google Scholar 

  • Stefani, M. M. A., Muller, I. & Louis, J. A. (1994) Leishmania major-specific CD8+ T cells are inducers and targets of nitric oxide produced by parasitized macrophages. Eur. J. Immunol. 24, 746–52.

    Google Scholar 

  • Taylor-Robinson, A. W., Liew, F. Y., Severn, A., XuDamo, Mcsorley, S. J., Garside, P., Padron, J. & Phillips, R. S. (1994) Regulation of the immune response of nitric oxide differentially produced by T helper type 1 and T helper type 2 cells. Eur. J. Immunol. 24, 980–4.

    Google Scholar 

  • Warren, J. B., Loi, R. K. & Coughlan, M. L. (1993) Involvement of nitric oxide synthase in the delayed vasodilator response to ultraviolet light irradiation of rat skin in vivo. Br. J. Pharm. 109, 802–6.

    Google Scholar 

  • WrenS. M., Hoffman, R. A., Billiar, T. R., AbouEl Ezz, A., Hronakes, M. L. & Ildstad, S. T. (1992) T-cell mitogenic responses in fully xenogeneic chimeras (WF RAT → B10 mouse) are restored by blocking the l-arginine-dependent nitric oxide pathway. Trans. Proc. 24, 499–500.

    Google Scholar 

  • Wright, C. E., Rees, D. D. & Moncada, S. (1992) Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc. Res. 26, 48–57.

    Google Scholar 

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Cattell, V., Jansen, A. Inducible nitric oxide synthase in inflammation. Histochem J 27, 777–784 (1995). https://doi.org/10.1007/BF00171758

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