title: Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.
abstract: Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice.
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maillet
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France Genetics Department, Regional Hospital, 14 Avenue de l'Hôpital, 45100 Orleans, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Perche
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pâris
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Richard
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gombault
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Ameziane
authors.initials: A
authors.lastname: Herzine
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Pichon
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Avenue E. Mounier, 53 bte B1.52.12, B-1200 Bruxelles, Belgium.
authors.forename: Francois
authors.initials: F
authors.lastname: Huaux
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mortaud
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
authors.forename: Valérie F J
authors.initials: VF
authors.lastname: Quesniaux
authors.affiliation: UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France celine.dubourg@cnrs-orleans.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Montécot-Dubourg
mesh_terms: D000613:Aminobutyrates / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D018698:Glutamic Acid / Q000276:immunology*; D006540:Herbicides / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D009195:Peroxidase / Q000235:genetics / Q000276:immunology; D011014:Pneumonia / Q000209:etiology / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: D000613:Aminobutyrates; D006540:Herbicides; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C003121:phosphinothricin; D016202:N-Methylaspartate; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II
keywords: IL1β; glufosinate ammonium; glutamate receptors; inflammation; lung; pesticide