PMID- 17506853 OWN - NLM STAT- MEDLINE DCOM- 20071109 LR - 20181113 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 122 IP - 2 DP - 2007 Oct TI - Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling. PG - 268-78 AB - Allergic asthma is a serious multifaceted disease characterized by eosinophil-rich airway inflammation, airway hyperreactivity and airway wall modifications known as remodelling. We previously demonstrated that the spores of two allergenic moulds, Alternaria alternata and Cladosporium herbarum, were potent inducers of immunoglobulin E (IgE) production. Moreover, mice sensitized by two intraperitoneal injections before intranasal challenge with A. alternata or C. herbarum spores developed an allergic lung inflammation and hyperreactivity. Here we report on the effect of chronic intranasal administration of C. herbarum spores or A. alternata extracts to unsensitized BALB/c mice. Our results demonstrate that this chronic treatment led to an increase of total serum IgE and the appearance of specific IgE and IgG1. Total cell number in bronchoalveolar lavage fluid from treated mice was highly increased compared to phosphate-buffered-saline-treated mice because of the accumulation of macrophages, neutrophils, lymphocytes and eosinophils. Airway hyperreactivity appeared after 3 weeks (extract) and 7 weeks (spores) and was maintained during the whole treatment. Increased interleukin-13 mRNA expression in the lungs and T helper type 2 cytokines (interleukin-4, -5, -6 and -13) and transforming growth factor-beta secretion in bronchoalveolar lavage fluid were also observed. Lung hydroxyproline and fibronectin contents indicated increased fibrosis in mice treated with mould allergen. These observations were confirmed by histological analysis demonstrating airway wall remodelling and strong mucus production. These observations show that this model, using chronic intranasal administration of relevant particulate allergens, is an interesting tool for the study of mechanisms leading to allergic pulmonary diseases and lung remodelling. FAU - Denis, Olivier AU - Denis O AD - Allergology Unit, WIV-Pasteur Institute of Brussels, Brussels, Belgium. odenis@pasteur.be FAU - van den Brule, Sybille AU - van den Brule S FAU - Heymans, Julie AU - Heymans J FAU - Havaux, Xavier AU - Havaux X FAU - Rochard, Christelle AU - Rochard C FAU - Huaux, Francois AU - Huaux F FAU - Huygen, Kris AU - Huygen K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070516 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antibodies, Fungal) RN - 0 (Cytokines) RN - 0 (Immunoglobulin G) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Administration, Intranasal MH - Alternaria/immunology MH - Animals MH - Antibodies, Fungal/biosynthesis MH - Asthma/*immunology/pathology MH - Bronchial Hyperreactivity/*immunology/pathology MH - Bronchoalveolar Lavage Fluid/cytology MH - Cladosporium/immunology MH - Cytokines/biosynthesis MH - Disease Models, Animal MH - Female MH - Immunoglobulin E/biosynthesis MH - Immunoglobulin G/biosynthesis MH - Lung/immunology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Spores, Fungal/*immunology MH - Th2 Cells/immunology PMC - PMC2265999 EDAT- 2007/05/18 09:00 MHDA- 2007/11/10 09:00 PMCR- 2008/10/01 CRDT- 2007/05/18 09:00 PHST- 2007/05/18 09:00 [pubmed] PHST- 2007/11/10 09:00 [medline] PHST- 2007/05/18 09:00 [entrez] PHST- 2008/10/01 00:00 [pmc-release] AID - IMM2636 [pii] AID - 10.1111/j.1365-2567.2007.02636.x [doi] PST - ppublish SO - Immunology. 2007 Oct;122(2):268-78. doi: 10.1111/j.1365-2567.2007.02636.x. Epub 2007 May 16.