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 mRNA isolated from PMN stimulated with IFN-gamma only, or with IFN-gamma plus either TNF-alpha or LPS, had similar half-lives. Finally, we found that interleukin-10, a known inhibitor of chemokine production in PMN, moderately suppressed the extracellular production of IP-10 in neutrophils stimulated with IFN-gamma plus either LPS or TNF-alpha. 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.
Cassatella
M A
MA
Department of General Pathology, University of Verona, Italy. MCNCSS@borgoroma.univr.it
Gasperini
S
S
Calzetti
F
F
Bertagnin
A
A
Luster
A D
AD
McDonald
P P
PP
D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003609:Dactinomycin; D007371:Interferon-gamma