Advertisement

The Role of Superoxide Nitric Oxide and Peroxynitrite in Neutrophil-Mediated Human Microvascular Cell Injury

  • M. M. Hardy
  • A. G. Flickinger
  • C. S. Schasteen
  • U. S. Ryan
Part of the NATO ASI Series book series (NSSA, volume 281)

Abstract

Neutrophil-derived oxygen radicals have been implicated in many pathophysiological states, such as the tissue injury associated with inflammation, organ ischemia associated with thrombosis, adult respiratory distress syndrome, rheumatoid arthritis, atherosclerosis, and asthma. The identity of the oxygen species responsible for oxidative cell injury is still largely in dispute. Evidence suggests that it may differ for each disease state, depend on the intrinsic antioxidant defenses of the target cell and the mode of neutrophil activation. In this study, we show that peroxynitrite, formed upon the interaction of superoxide and nitric oxide, may be the primary toxic oxygen radical species generated in vitro by neutrophils primed with TNF-alpha, then stimulated with C5a or N-formyl-Met-Leu-Phe (fMLP). Phorbol myristate acetate (PMA) induced cell injury also appears to cause the generation of peroxynitrite, however, superoxide and hydrogen peroxide may also play a role. Immune complex induced injury appears not to be mediated by peroxynitrite in this system. Neutrophils stimulated by TNF-alpha/C5a, TNF- alpha/fMLP, or PMA generated superoxide and nitrate (a product of peroxynitrite decomposition), both of which correlated with human dermal microvascular endothelial (HDME) cell injury. The addition of authentic nitric oxide caused a dose-dependent amplification of injury only when the neutrophils were stimulated to generate superoxide and nitrate. Furthermore, superoxide dismutase (SOD) mimics or oxygemoglobin (oxyHb), a nitric oxide scavenger, attenuated TNF-alpha/C5a or TNF-alpha/fMLP stimulated neutrophil-mediated injury. PMA-induced cell injury was inhibited by SOD mimic or a combination of catalase and SOD mimic, but not oxyHb.

Keywords

Nitric Oxide Immune Complex Cell Injury Phorbol Myristate Acetate Airway Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Capman-Kirkland, E.S., Wasvary, J.S. and Seligmann, B.E., 1991, J. Immunol. Meth. 142: 95–104.CrossRefGoogle Scholar
  2. Damiani, P. and Burini, G., 1986, Talanta 33: 649–652.PubMedCrossRefGoogle Scholar
  3. Huie, R.E. and Padmaja, S. Free Rad. Res. Comm. 18: 195–199, 1993.CrossRefGoogle Scholar
  4. Ischiropoulos, H., Zhu, L., Chen, J., Tsai, M., Martin, J.C., Smith, C.D. and Beckman, J.S., 1992, Arch. Biochem. Biophys. 298: 431–437.PubMedCrossRefGoogle Scholar
  5. Look, D.C., Rapp, S.R., Keller, B.T. and Holtzman, M.J., 1992, Selective induction of intercellular adhesion molecule-1 by interferon-gamma in human airway epithelial cells. Am. J. Physiol. 263; L79–L87.PubMedGoogle Scholar
  6. Marks, R.M., Czerniecki, M. and Penny, R., 1985, Human dermal microvascular cells: an improved method for tissue culture and a description of some singular properties in culture. In: Vit. Cell. Devel. Biol. 21: 627–635.Google Scholar
  7. Misko, T.P., Moore, W.M., Kasten, T.P., Nickols, G.A., Corbett, J.A., Tilton, R.G., McDaniel, M.L., Williamson, J.R. and Currie, M.G., 1993, European J. Pharmacol. 233: 119–125.CrossRefGoogle Scholar
  8. Radi, R., Beckman, J.S., Bush, K.M. and Freeman, B.A., 1991, J. Biol. Chem. 266: 4244–4250.PubMedGoogle Scholar
  9. Radi, R., Beckman, J.S., Bush, K M. and Freeman, B.A., 1991, Arch. Biochem. Biophys. 288: 481–487.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • M. M. Hardy
    • 1
  • A. G. Flickinger
    • 1
  • C. S. Schasteen
    • 1
  • U. S. Ryan
    • 2
  1. 1.Department of Cardiovascular Disease ResearchG.D. Searle, Inc.St LouisUSA
  2. 2.T-Cell SciencesCambridgeUSA

Personalised recommendations