title: Lipopolysaccharide binding protein potentiates airway reactivity in a murine model of allergic asthma.
abstract: The development of allergic asthma is influenced by both genetic and environmental factors. Epidemiologic data often show no clear relationship between the levels of allergen and clinical symptoms. Recent data suggest that bacterial LPS may be a risk factor related to asthma severity. Airborne LPS is typically present at levels that are insufficient to activate alveolar macrophages in the absence of the accessory molecule LPS binding protein (LBP). LBP levels are markedly elevated in bronchoalveolar lavage fluids obtained from asthmatic subjects compared with those in normal controls. We hypothesized that LBP present in the lung could augment the pulmonary inflammation and airway reactivity associated with allergic asthma by sensitizing alveolar macrophages to LPS or other bacterial products and triggering them to release proinflammatory mediators. We compared wild-type (WT) and LBP-deficient mice using a defined Ag immunization and aerosol challenge model of allergic asthma. Immunized LBP-deficient mice did not develop substantial Ag-induced airway reactivity, whereas WT mice developed marked bronchoconstriction following aerosol Ag sensitization and challenge with methacholine. Similarly, production of NO synthase 2 protein and the NO catabolite peroxynitrite was dramatically higher in the lungs of WT mice following challenge compared with that in LBP-deficient mice. Thus, NO production appears to correlate with airway reactivity. In contrast, both mice developed similar pulmonary inflammatory cell infiltrates and elevated mucin production. Thus, LBP appears to participate in the development of Ag-induced airway reactivity and peroxynitrite production, but does not seem to be required for the development of pulmonary inflammation.
authors.affiliation: The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Strohmeier
authors.forename: J H
authors.initials: JH
authors.lastname: Walsh
authors.forename: E S
authors.initials: ES
authors.lastname: Klings
authors.forename: H W
authors.initials: HW
authors.lastname: Farber
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: D M
authors.initials: DM
authors.lastname: Center
authors.forename: M J
authors.initials: MJ
authors.lastname: Fenton
mesh_terms: D000209:Acute-Phase Proteins; D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000276:Adjuvants, Immunologic; D000336:Aerosols; D000485:Allergens; D002352:Carrier Proteins; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009566:Nitrates; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin; D000099231:Lipopolysaccharide-Binding Protein; C039642:peroxynitric acid; C496317:Nos2 protein, mouse