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Title: IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production
Authors: Verri Jr., W.A.
Cunha, T.M.
Ferreira, S.H.
Wei, X.
Leung, B.P. 
Fraser, A.
McInnes, I.B.
Liew, F.Y.
Cunha, F.Q.
Keywords: Autoimmunity
Rheumatoid arthritis
Issue Date: Dec-2007
Source: Verri Jr., W.A., Cunha, T.M., Ferreira, S.H., Wei, X., Leung, B.P., Fraser, A., McInnes, I.B., Liew, F.Y., Cunha, F.Q. (2007-12). IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. European Journal of Immunology 37 (12) : 3373-3380. ScholarBank@NUS Repository.
Abstract: We have investigated the mechanisms underlying IL-15-induced neutrophil migration into inflamed tissues. IL-15 induced neutrophil migration to the peritoneal cavity in mice in a time- and dose-dependent manner. The cell migration was not induced in IL-18 -/-, MIP-1α (CCL3) -/-, TNFR1 -/- or 5-LOX -/- mice but was normal in IFN-γ -/- mice. IL-15-induced neutrophil migration was inhibited by anti-MIP-2 (CXCL2) antibody or MK886 (leukotriene synthesis inhibitor). IL-18-induced neutrophil migration was also dependent on TNFR1, MIP-1α, MIP-2 and leukotriene. Consistent with this observation, IL-15 induced IL-18 production, and IL-15 or IL-18 injection induced the production of MIP-2, MIP-1α, TNF-α and LTB 4. In an antigen-specific inflammation model, ovalbumin (OVA)-induced neutrophil migration was completely inhibited by soluble IL-15Rα (sIL-15Rα) or anti-MIP-2 antibody. Furthermore, cell migration was absent in IL-18 -/-, MIP-1α -/-, TNFR1 -/-, or 5-LOX -/- mice. OVA challenge induced the release of MIP-2, MIP-1α, TNF-α and LTB 4 in the peritoneal cavity in an IL-15- and IL-18-dependent manner. We also found that neutrophils from the peripheral blood and synovial fluid of patients with rheumatoid arthritis produced substantial amounts of IL-18 and LTB 4 following activation by IL-15. Together, these results demonstrate that IL-15 plays an important role in antigen-induced neutrophil migration during inflammation, triggering a sequential OVA, IL-15, IL-18, MIP-2, MIP-1α, TNF-α, LTB 4 and neutrophil migration signaling cascade. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: European Journal of Immunology
ISSN: 00142980
DOI: 10.1002/eji.200737488
Appears in Collections:Staff Publications

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