title: The presence of LPS in OVA inhalations affects airway inflammation and AHR but not remodeling in a rodent model of asthma.
abstract: Ovalbumin (OVA) is the most frequently used allergen in animal models of asthma. Lipopolysaccharide (LPS) contaminating commercial OVA may modulate the evoked airway inflammatory response to OVA. However, the effect of LPS in OVA on airway remodeling, especially airway smooth muscle (ASM) has not been evaluated. We hypothesized that LPS in commercial OVA may enhance allergen-induced airway inflammation and remodeling. Brown Norway rats were sensitized with OVA on day 0. PBS, OVA, or endotoxin-free OVA (Ef-OVA) was instilled intratracheally on days 14, 19, 24. Bronchoalveolar lavage (BAL) fluid, lung, and intrathoracic lymph node tissues were collected 48 h after the last challenge. Immunohistochemistry for α-smooth muscle actin, Periodic-Acid-Schiff staining, and real-time qPCR were performed. Airway hyperresponsiveness (AHR) was also measured. BAL fluid macrophages, eosinophils, neutrophils, and lymphocytes were increased in OVA-challenged animals, and macrophages and neutrophils were significantly lower in Ef-OVA-challenged animals. The ASM area in larger airways was significantly increased in both OVA and Ef-OVA compared with PBS-challenged animals. The mRNA expression of IFN-γ and IL-13 in lung tissues and IL-4 in lymph nodes was significantly increased by both OVA and Ef-OVA compared with PBS and were not significantly different between OVA and Ef-OVA. Monocyte chemoattractant protein (MCP)-1 in BAL fluid and AHR were significantly increased in OVA but not in Ef-OVA. LPS contamination in OVA contributes to the influx of macrophages and MCP-1 increase in the airways and to AHR after OVA challenges but does not affect OVA-induced Th1 and Th2 cytokine expression, goblet cell hyperplasia, and ASM remodeling.
authors.affiliation: Meakins Christie Laboratories, 3626 St Urbain, Montreal, Québec, Canada, H2X 2P2.
authors.forename: Kimitake
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Sana
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Paul-André
authors.initials: PA
authors.lastname: Risse
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Hirota
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects* / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology; D054360:Chemokine CXCL1 / Q000276:immunology; D004195:Disease Models, Animal; D004340:Drug Contamination; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D006965:Hyperplasia / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D018793:Interleukin-13; D008070:Lipopolysaccharides; D016328:NF-kappa B; D007371:Interferon-gamma; D010047:Ovalbumin; C483803:Egfr protein, rat; D066246:ErbB Receptors