Regulated production of the interferon‐γ‐inducible protein−10 (IP‐10) chemokine by human neutrophils

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Abstract
Interferon‐γ (IFN‐γ)‐inducible protein‐10 (IP‐10), a member of the C‐X‐C sub‐family of chemokines, is known to be produced by monocytes, lymphocytes, keratinocytes and endothelial cells in response to IFN‐γ Here, we show that human polymorphonuclear neutrophils (PMN) also have the ability to produce IP‐10. IFN‐γ alone had a modest effect on IP‐10 mRNA accumulation, whereas tumor necrosis factor‐α (TNF‐α), yeast particles opsonized with IgG (Y‐IgG), lipopolysaccharide (LPS), and formyl‐methionyl‐leucyl‐phenylalanine (fMLP) all failed to up‐regulate IP‐10 gene expression. However, stimulation of neutrophils with IFN‐γ in combination with either TNF‐α or LPS (but not with Y‐IgG or fMLP) resulted in a considerable induction of IP‐10 mRNA transcripts, as well as in the extracellular release of the protein. In contrast, the best inducer of IP‐10 release from peripheral blood mononuclear cells was IFN‐γ alone. Furthermore, mRNA stabilization analyses demonstrated that IP‐10 mRNA isolated from PMN stimulated with IFN‐γ only, or with IFN‐γ plus either TNF‐α or LPS, had similar half‐lives. Finally, we found that interleukin‐10, a known inhibitor of chemokine production in PMN, moderatley suppressed the extracellular production of IP‐10 in neutrophils stimulated with IFN‐γ plus either LPS or TNF‐α. Since IP‐10 is a potent chemoattractant for activated T lymphocytes, the ability of neutrophils to produce IP‐10 might contribute to the evolution and progression of the inflammatory response.