Generation of Nitric Oxide by Mouse Dendritic Cells and Its Implications for Immune Response Regulation

  • C. Andrew Bonham
  • Lina Lu
  • Rosemary A. Hoffman
  • Richard L. Simmons
  • Angus W. Thomson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)


Nitric oxide (NO) is a ubiquitous compound produced by the oxidative metabolism of L-arginine.1 A variety of functions have been ascribed to it, including neurotransmission, and mediation of smooth muscle relaxation.2.3 In the immune system, NO is involved in tumoricidal and microbicidal activity, and inhibition of T cell proliferation.4–7 There are at least three isoforms of nitric oxide synthase (NOS), the cell type-specific enzyme which produces NO.8 In cells of the immune system, such as macrophages and neutrophils, NOS activity is induced by a number of proinflammatory mediators such as IFN-γ, IL-1, TNF-α, and microbial cell wall products, such as BCG and LPS.9.10 Dendritic cells (DC) are the most potent known antigen presenting cells capable of activating naive T cells.11 Mature DC in secondary lymphoid tissues express high levels of major histocompatibility complex (MHC) and costimulatory molecules. DC residing in nonlymphoid tissue, such as the Langerhans cells in the dermis, typically express lower levels of these molecules. However, in response to stress (such as LPS or inflammatory cytokines), these ‘immature’ cells migrate to T dependent areas in lymphoid tissue, and upregulate expression of MI-IC and costimulatory molecules.12,13 Macrophages, which may share a common ontogeny with DC, respond to these cytokines in part by the generation of nitric oxide.9 However, there are no reports of NO production by DC stimulated by cytokine or LPS. In this study we present evidence that purified mouse bone marrow-derived DC express an inducible NOS which produces NO in response to IFN-γ, LPS, or upon interaction with allogeneic T cells. The synthesis of NO is associated with apoptosis in the DC, and inhibition of proliferation of allogeneic T cells.


Nitric Oxide Costimulatory Molecule Mixed Leukocyte Reaction Dendritic Cell Culture Mouse Dendritic Cell 
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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • C. Andrew Bonham
    • 1
  • Lina Lu
    • 1
  • Rosemary A. Hoffman
    • 1
  • Richard L. Simmons
    • 1
  • Angus W. Thomson
    • 1
    • 2
  1. 1.Department of SurgeryUniversity of PittsburghPittsburghUSA
  2. 2.Department of Molecular Genetics and BiochemistryUniversity of PittsburghPittsburghUSA

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