IL‐15 mediates antigen‐induced neutrophil migration by triggering IL‐18 production

European Journal of Immunology - Tập 37 Số 12 - Trang 3373-3380 - 2007
Waldiceu A. Verri1, Thiago M. Cunha1, Fernando Q. Cunha1, Xiao–Qing Wei2, Bernard P. Leung3,2, Alasdair R. Fraser2, Iain B. McInnes2, Foo Y. Liew2
1Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil,
2Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK
3Department of Physiology, National University of Singapore, Singapore

Tóm tắt

AbstractWe 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 LTB4. 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 LTB4 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 LTB4 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, LTB4 and neutrophil migration signaling cascade.

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Thông tin xuất bản

European Journal of Immunology

Tập 37 Số 12

3373-3380

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