title: IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes.
abstract: BACKGROUND
  IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have been shown to express complementary and partially overlapping roles, it is not clear whether a similar IgE/TNF-α/MMP-9 axis exists in the human basophil. The purpose of this study was thus to investigate whether IgE-mediated activation of human basophils induces TNF-α and MMP-9 release.
  
  
  METHODS
  Human peripheral blood mononuclear cells (PBMC), isolated basophils and monocytes were stimulated up to 21 h with anti-IgE. Mediator releases were assessed by ELISA, and surface expressions of mediators were detected by flow cytometry. Upregulation of cytokine production was detected by Western blot and polymerase chain reaction (PCR).
  
  
  RESULTS
  IgE-mediated activation of basophils induced the synthesis and release of both TNF-α and MMP-9 from PBMC. In contrast, IgE-mediated activation of purified basophils induced the release and cellular expression of TNF-α but not MMP-9. Isolated monocytes did not release MMP-9 upon anti-IgE stimulation, but MMP-9 release was induced by stimulating monocytes with supernatants from activated basophils, and this release was inhibited by anti-TNF-α neutralizing antibodies.
  
  
  CONCLUSIONS
  Our results strongly indicate that human basophils release TNF-α following IgE-dependent activation and that this cytokine subsequently stimulates MMP-9 release from monocytes. These findings support a direct involvement of basophils in inflammation as well as suggesting a role for the basophil in tissue remodelling.
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, 5000 Odense C, Denmark. sfal@reflab.dk
authors.forename: S
authors.initials: S
authors.lastname: Falkencrone
authors.forename: L K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: C
authors.initials: C
authors.lastname: Bindslev-Jensen
authors.forename: A
authors.initials: A
authors.lastname: Woetmann
authors.forename: N
authors.initials: N
authors.lastname: Odum
authors.forename: B C
authors.initials: BC
authors.lastname: Poulsen
authors.forename: L
authors.initials: L
authors.lastname: Blom
authors.forename: B M
authors.initials: BM
authors.lastname: Jensen
authors.forename: B F
authors.initials: BF
authors.lastname: Gibbs
authors.forename: I M
authors.initials: IM
authors.lastname: Yasinska
authors.forename: V V
authors.initials: VV
authors.lastname: Sumbayev
authors.forename: P S
authors.initials: PS
authors.lastname: Skov
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D014409:Tumor Necrosis Factor-alpha; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D020780:Matrix Metalloproteinase 9