| First Author | Verri WA Jr | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 12 | Pages | 3373-80 |
| PubMed ID | 17979156 | Mgi Jnum | J:128427 |
| Mgi Id | MGI:3767105 | Doi | 10.1002/eji.200737488 |
| Citation | Verri WA Jr, et al. (2007) IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol 37(12):3373-80 |
| abstractText | 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-1alpha (CCL3)(-/-), TNFR1(-/-) or 5-LOX(-/-) mice but was normal in IFN-gamma(-/-) 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-1alpha, 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-1alpha, TNF-alpha and LTB(4). In an antigen-specific inflammation model, ovalbumin (OVA)-induced neutrophil migration was completely inhibited by soluble IL-15Ralpha (sIL-15Ralpha) or anti-MIP-2 antibody. Furthermore, cell migration was absent in IL-18(-/-), MIP-1alpha(-/-), TNFR1(-/-), or 5-LOX(-/-) mice. OVA challenge induced the release of MIP-2, MIP-1alpha, TNF-alpha 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-1alpha, TNF-alpha, LTB(4) and neutrophil migration signaling cascade. |
