title: IgE immune complexes stimulate an increase in lung mast cell progenitors in a mouse model of allergic airway inflammation.
abstract: Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 10(6) mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcRγ deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcRγ chain. This most likely takes place via activation of FcεRI, although activation via FcγRIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Joakim S
authors.initials: JS
authors.lastname: Dahlin
authors.forename: Martin A
authors.initials: MA
authors.lastname: Ivarsson
authors.forename: Birgitta
authors.initials: B
authors.lastname: Heyman
authors.forename: Jenny
authors.initials: J
authors.lastname: Hallgren
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000503:physiopathology*; D007073:Immunoglobulin E / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D013234:Stem Cells / Q000276:immunology* / Q000473:pathology; D014132:Trachea / Q000473:pathology*
chemical_list: D007073:Immunoglobulin E