Immune Defence: Role of Reactive Nitrogen Intermediates


Nitric oxide (NO) represents a ubiquitous intercellular messenger regulating a plethora of physiological processes such as vasculature homeostasis and neurotransmission. In addition, NO plays a fundamental role in immune responses, acting as either an immune‐stimulatory or immunosuppressive mediator. NO‐mediated effects have been traditionally classified into direct and indirect responses. Indeed, in physiopathological conditions, NO can directly interact with the biological targets or instead it can form reactive intermediates by reacting with either O2 molecule or O2 superoxide anion. Both direct and indirect NO‐mediated effects play a pivotal role in immune responses against pathogens and in cancer. The chemistry of NO/RNOS (reactive nitrogen oxide species) in host immunity so far represents an attractive field to be investigated. In this article, we propose to discuss earlier and recent evidences that shed light on this issue.

Key Concepts

  • Nitric oxide and reactive nitrogen species participate in numerous biological processes, both in physiological and pathological conditions.
  • Nitric oxide and reactive nitrogen species mediate either direct or indirect biological effects in immune responses.
  • Nitric oxide and reactive nitrogen species play a key role in bacterial, viral and parasite infections.
  • Different stages of carcinogenesis are influenced by nitric oxide and reactive nitrogen species.
  • The understanding of nitric oxide dynamics in neoplastic tissues will be instrumental for the definition of novel therapies.

Keywords: nitric oxide; reactive nitrogen and oxygen species; immunity; inflammation; cancer

Figure 1. Chemical biology of nitric oxide. This scheme represents the basic reactions that nitric oxide undergoes in biological systems. At low concentrations, reactions where NO reacts directly with its substrate are referred to as ′direct effects′. Indirect effects result from the reaction of NO with either oxygen or superoxide to produce intermediates that mediate either oxidative or nitrosative stress.
Figure 2. NO/RNOS in cancer progression. The figure depicts the role of NO/RNOS during a multistage model of carcinogenesis, involving initiation, latency, promotion and progression. High or low concentration of NO/RNOS mediates multiple effects on both tumour and immune cells, which are schematically represented in the figure.


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Molon, Barbara, Agnellini, Andrielly HR, Wink, David A, Citrin, Deborah, Vitek, Michael P, Colton, Carol, Pacelli, Roberto, Ogawa, Rygeio, Thomas, Douglas D, Miranda, Katrina M, and Espey, Michael G(Jun 2017) Immune Defence: Role of Reactive Nitrogen Intermediates. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000484.pub2]