Gene expression and production of the monokine induced by IFN-gamma (MIG),IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils

Monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattrac tant (I-TAC), and IFN-gamma-inducible protein of 10 kDa (IP-10) are related members of the CXC chemokine subfamily that bind to a common receptor, CXC R3, and that are produced by different cell types in response to IFN-gamma. We have recently reported that human polymorphonuclear neutrophils (PMN) h ave the capacity to release IP-10, Herein, we show. that PMN also hare the ability to produce MIG; and to express I-TAC mRNA in response to IFN-gamma in combination with either TNF-alpha or LPS. While IFN-gamma, alone or in a ssociation with agonists such as fMLP, IL-8, granulocyte (G)-CSF and granul ocyte-macrophage (GM)-CSF, failed to influence MIG, IP-10, and I-TAC gene e xpression, IFN-alpha, in combination with TNF-alpha, LPS, or IL-1 beta. res ulted in a considerable induction of IP-10 release by neutrophils. Furtherm ore, IL-10 and IL-4 significantly suppressed the expression of MIG, IP-10, and I-TAC mRNA and the extracellular production of MIG and IP-10 in neutrop hils stimulated with IFN-gamma plus either I-PS or TNF-alpha. Finally, supe rnatants harvested from stimulated PMN induced migration and rapid integrin -dependent adhesion of CXCR3-expressing lymphocytes; these activities were significantly reduced by neutralizing anti-MIG and anti-IP-10 Abs, suggesti ng that they were mediated by MIG and IP-10 present in the supernatants, Si nce MIG, IP-10, and I-TAC are potent chemoattractants for NK cells and Th1 lymphocytes, the ability of neutrophils to produce these chemokines might c ontribute not only. to the progression and evolution of the inflammatory re sponse, but also to the regulation of the immune response.