Regulated production of the interferon-gamma-inducible protein-10 (IP-10) chemokine by human neutrophils

Interferon-gamma (IFN-gamma)-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-gamma. Here, we show that human polymorphonuclear neutrophils (PMN) also have the ability to produce IP-10. IFN-gamma alone had a modest effect on IP-10 mRNA accumulation, whereas tumor necrosis factor-alpha (TNF-alpha), 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-gamma in combination with either TNF-alpha 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-gamma alone. Furthermore, mRNA stabilization analyses demonstrated that IP-10