title: Influence of the macrophage bacterial resistance gene, Nramp1 (Slc11a1), on the induction of allergic asthma in the mouse.
abstract: Based on the hygiene hypothesis that lack of early childhood bacterial infections would favor development of allergic disease, we hypothesize that genes controlling antibacterial resistance may be important as well. We, therefore, studied whether Nramp1 alleles that determine resistance (Nramp1r) or susceptibility (Nramp1s) to intracellular bacteria at the macrophage level affect sensitivity to induction of allergic asthma. Nramp1s and congenic Nramp1r mice were sensitized with ovalbumin/alum on days 0 and 14 and challenged with ovalbumin or saline aerosols on days 42, 45, and 48. On day 49, airway responsiveness was assessed, blood was withdrawn, and lung lavage was performed. We demonstrated that ovalbumin sensitization and challenge of Nramp1s and Nramp1r mice caused comparable airway hyperreactivity and airway eosinophilia and a similar increase in serum levels of ovalbumin-specific IgG1 and IgG2a. Ovalbumin challenge, however, induced significantly lower serum levels of total and ovalbumin-specific IgE and significantly lower mast cell degranulation in Nramp1r mice as compared with Nramp1s mice. In addition, ovalbumin challenge of Nramp1r mice led to significantly less release of Th2 cytokines into the airways. Results show that Nramp1 can affect the development of allergy but not the development of airway hyperresponsiveness in the mouse.
authors.affiliation: Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Smit
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
authors.forename: Maarten O
authors.initials: MO
authors.lastname: Hoekstra
authors.forename: Frans P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: Nanne
authors.initials: N
authors.lastname: Bloksma
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D015550:Cell Degranulation; D053818:Chymases; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008407:Mast Cells / Q000201:enzymology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012697:Serine Endopeptidases / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D053818:Chymases; D007073:Immunoglobulin E; D016753:Interleukin-10; D018793:Interleukin-13; D015847:Interleukin-4; D015848:Interleukin-5; D010047:Ovalbumin; D012697:Serine Endopeptidases; D000099173:Natural Resistance-associated Macrophage Protein 1