title: Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1.
abstract: Antibody-antigen interactions in the airway initiate inflammation in acute asthma exacerbations. This inflammatory response is characterized by the recruitment of granulocytes into the airways. In murine models of asthma, granulocyte recruitment into the lung contributes to the development of airway hyperresponsiveness (AHR), mucus production, and airway remodeling. Leukotriene B4 is a mediator released following antigen challenge that has chemotactic activity for granulocytes, mediated through its receptor, BLT1. We investigated the role of BLT1 in granulocyte recruitment following antigen challenge. Wild-type mice and BLT1-/- mice were sensitized and challenged with ovalbumin (OVA) to induce acute allergic airway inflammation. In addition, to explore the relevance to antibody-antigen interactions, we injected OVA bound to anti-OVA IgG1 or anti-OVA IgE intratracheally into naïve wild-type and BLT1-/- mice. Cell composition of the lungs, cytokine levels, histology, and AHR were determined. After sensitization and challenge with ovalbumin, there was significantly reduced neutrophil and eosinophil recruitment into the airways of BLT1-/- mice compared with wild-type animals after one or two daily antigen challenges, but this difference was not seen after three or four daily antigen challenges. Mucus production and AHR were not affected. Intratracheal injection of OVA bound to IgG1 or IgE induced neutrophil recruitment into the airways in wild-type mice but not in the BLT1-/- mice. We conclude that BLT1 mediates early recruitment of granulocytes into the airway in response to antigen-antibody interactions in a murine model of acute asthma.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.forename: Ryan
authors.initials: R
authors.lastname: Jackobek
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D001249:Asthma / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D006098:Granulocytes / Q000473:pathology*; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018102:Receptors, Leukotriene B4 / Q000172:deficiency / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D018925:Chemokines; D007074:Immunoglobulin G; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D007073:Immunoglobulin E; D010047:Ovalbumin