Nitrite Generation in Interleukin-4—Treated Human Macrophage Cultures Does Not Involve the Nitric Oxide Synthase Pathway

Schneemann, M. ; Schoedon, G. ; Linscheid, P. ; Walter, R. ; Blau, N. ; Schaffner, A.

In: Journal of Infectious Diseases, 1997, vol. 175, no. 1, p. 130-135

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    Summary
    The search continues for high-output nitric oxide biosynthesis in human macrophages analogous to murine phagocytes. Recently, generation of nitrite in culture supernatants of human macrophages exposed to interferon-γ and interleukin-4 (IFN-γ/IL-4) was reported. The present study reproduces these findings and shows that L-arginine is not consumed and L-citrulline is not produced during this process. Furthermore, the biosynthesis of the obligatory cofactor tetrahydrobiopterin is not coinduced. These biochemical data provide support against a nitric oxide synthase contribution to nitrite accumulation. Nitrite was generated from nitrate salts even in cell-free media. Nitric oxide synthase activity but not nitrate reduction depended on molecular oxygen. Nitrite accumulation in experiments with IFN-γ/IL-4 in human monocytes appears to be an in vitro artifact produced by nitrate-reducing activities contained in cytokine preparations