title: Allergic sensitization is associated with inadequate antioxidant responses in mice and men.
abstract: BACKGROUND
  Allergies arise from aberrant Th2 responses to allergens. The processes involved in the genesis of allergic sensitization remain elusive. Some allergens such as derived from house dust mites have proteolytic activity which can induce oxidative stress in vivo. A reduced capacity of the host to control oxidative stress might prime for allergic sensitization.
  
  
  METHODS
  Two different strains of mice were compared for their antioxidant and immune response to HDM. Protease activity of the HDM extract was reduced to investigate its role in oxidative stress induction in the airways and whether this induction could determine allergic sensitization and inflammation. The role of oxidative stress in allergic sensitization was also investigated in humans. An occupational cohort of animal workers was followed for the development of sensitization to rodent urinary proteins. Levels of oxidative stress in serum and antioxidant responses by PBMCs were determined.
  
  
  RESULTS
  Susceptibility to allergic sensitization to mite allergens in mice was highly dependent on host genetic background and was associated with oxidative stress in the lungs before allergen exposure and poor antioxidant response after allergen exposure. Reduction in mite protease activity limited its capacity to induce oxidative stress and allergic inflammation in mice. We showed that also in human subjects, oxidative stress before allergen exposure and poor antioxidant responses were associated with predisposition to occupational allergy.
  
  
  CONCLUSIONS
  Our study indicates that oxidative stress condition before allergen exposure due to an inadequate antioxidant response may prime for allergic Th2 responses.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Utsch
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Respiratory Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Folisi
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Akkerdaas
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Logiantara
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Respiratory Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van de Pol
authors.affiliation: Department of Respiratory Medicine, OLVG, Amsterdam, the Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: van der Zee
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Krop
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Respiratory Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Otorhinolaryngology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Ree
authors.affiliation: Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: L S
authors.initials: LS
authors.lastname: van Rijt
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010447:Peptide Hydrolases / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D000485:Allergens; D000975:Antioxidants; D016207:Cytokines; D051267:NF-E2-Related Factor 2; D051197:Toll-Like Receptor 4; D051547:Heme Oxygenase-1; D010447:Peptide Hydrolases
keywords: 4-hydroxynonenal; allergic sensitization; house dust mite; oxidative stress; rodent urinary proteins