title: Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of asthma.
abstract: Lung mastocytosis and antigen-induced bronchoconstriction are common features in allergic asthmatics. It is therefore important that animal models of asthma show similar features of mast cell inflammation and reactivity to inhaled allergen. We hypothesized that house dust mite (HDM) would induce mastocytosis in the lung and that inhalation of HDM would trigger bronchoconstriction. Mice were sensitized with intranasal HDM extract, and the acute response to nebulized HDM or the mast cell degranulating compound 48/80 was measured with respiratory input impedance. Using the constant-phase model we calculated Newtonian resistance (Rn) reflecting the conducting airways, tissue dampening (G), and lung elastance (H). Bronchoalveolar lavage fluid was analyzed for mouse mast cell protease-1 (mMCP-1). Lung tissue was analyzed for cytokines, histamine, and α-smooth muscle actin (α-SMA), and histological slides were stained for mast cells. HDM significantly increased Rn but H and G remained unchanged. HDM significantly expanded mast cells compared with control mice; at the same time mMCP-1, α-SMA, Th2 cytokines, and histamine were significantly increased. Compound 48/80 inhalation caused bronchoconstriction and mMCP-1 elevation similarly to HDM inhalation. Bronchoconstriction was eliminated in mast cell-deficient mice. We found that antigen-induced acute bronchoconstriction has a distinct phenotype in mice. HDM sensitization caused lung mastocytosis, and we conclude that inhalation of HDM caused degranulation of mast cells leading to an acute bronchoconstriction without affecting the lung periphery and that mast cell-derived mediators are responsible for the development of the HDM-induced bronchoconstriction in this model.
authors.affiliation: Dept. of Medicine, The Univ. of Vermont, Vermont Lung Center, HSRF, Rm. 230, 149 Beaumont Ave., Burlington, VT 05405-0075. lennart.lundblad@uvm.edu.
authors.forename: Shannon
authors.initials: S
authors.lastname: Li
authors.forename: Minara
authors.initials: M
authors.lastname: Aliyeva
authors.forename: Nirav
authors.initials: N
authors.lastname: Daphtary
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Martin
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.forename: Shannon F
authors.initials: SF
authors.lastname: Kostin
authors.forename: Jos L
authors.initials: JL
authors.lastname: van der Velden
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Hyman
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stevenson
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Phillips
authors.forename: Lennart K A
authors.initials: LK
authors.lastname: Lundblad
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000494:pharmacology; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D008415:Mastocytosis / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D039981:Pyroglyphidae / Q000276:immunology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D000941:Antigens; D003189:p-Methoxy-N-methylphenethylamine
keywords: histamine; input impedance; mast cell protease-1