title: Mast cell-derived mediators promote murine neutrophil effector functions.
abstract: Mast cells are able to trigger life-saving immune responses in murine models for acute inflammation. In such settings, several lines of evidence indicate that the rapid and protective recruitment of neutrophils initiated by the release of mast cell-derived pro-inflammatory mediators is a key element of innate immunity. Herein, we investigate the impact of mast cells on critical parameters of neutrophil effector function. In the presence of activated murine bone marrow-derived mast cells, neutrophils freshly isolated from bone marrow rapidly lose expression of CD62L and up-regulate CD11b, the latter being partly driven by mast cell-derived TNF and GM-CSF. Mast cells also strongly enhance neutrophil phagocytosis and generation of reactive oxygen species. All these phenomena partly depend on mast cell-derived TNF and to a greater extend on GM-CSF. Furthermore, spontaneous apoptosis of neutrophils is greatly diminished due to the ability of mast cells to deliver antiapoptotic GM-CSF. Finally, we show in a murine model for acute lung inflammation that neutrophil phagocytosis is impaired in mast cell-deficient Kit (W-sh) /Kit (W-sh) mice but can be restored upon mast cell engraftment. Thus, a previously underrated feature of mast cells is their ability to boost neutrophil effector functions in immune responses.
authors.affiliation: Institute for Immunology, University Medical Center, Mainz, Germany.
authors.forename: Fatma
authors.initials: F
authors.lastname: Doener
authors.forename: Anastasija
authors.initials: A
authors.lastname: Michel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reuter
authors.forename: Pamela
authors.initials: P
authors.lastname: Friedrich
authors.forename: Livia
authors.initials: L
authors.lastname: Böhm
authors.forename: Manfred
authors.initials: M
authors.lastname: Relle
authors.forename: Laura
authors.initials: L
authors.lastname: Codarri
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Markus Philipp
authors.initials: MP
authors.lastname: Radsak
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
authors.forename: Marc
authors.initials: M
authors.lastname: Becker
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018375:Neutrophil Activation / Q000235:genetics; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000235:genetics; D011014:Pneumonia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: cell activation; inflammation; lung; mast cells; neutrophils; rodent