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Published ahead of print on December 1, 2005, doi:10.1164/rccm.200503-466OC
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 512-518, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200503-466OC


Original Article

Intranasal Exposure to Stachybotrys chartarum Enhances Airway Inflammation in Allergic Mice

Marina S. Leino, Harri T. Alenius, Nanna Fyhrquist-Vanni, Henrik J. Wolff, Kari E. Reijula, Eeva-Liisa Hintikka, Mirja S. Salkinoja-Salonen, Tari Haahtela and Mika J. Mäkelä

Finnish Institute of Occupational Health; Department of Pathology and Department of Allergy, Helsinki University Central Hospital; Uusimaa Regional Institute of Occupational Health; Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki; and Kymenlaakso Central Hospital, Kotka, Finland

Correspondence and requests for reprints should be addressed to Marina Leino, M.Sc., Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250, Helsinki, Finland. E-mail: marina.leino{at}ttl.fi

Rationale: Exposure to building dampness, often associated with growth of microbes such as Stachybotrys chartarum, has been linked to respiratory symptoms. We have shown previously in a murine model that exposure to S. chartarum can induce lung inflammation characterized by infiltration of neutrophils and lymphocytes; this process is regulated by proinflammatory cytokines and leucocyte-attracting chemokines.

Objectives: Because an atopic predisposition may influence the response to microbes, we examined the effects of S. chartarum on allergic mice in an experimental model. BALB/c mice were sensitized to ovalbumin by intraperitoneal injections and exposed for 3 wk to spores of S. chartarum.

Measurements and Main Results: Numbers of eosinophils and neutrophils were drastically increased in bronchoalveolar fluid from these mice as compared with the ovalbumin-sensitized/challenged mice or those exposed to S. chartarum without ovalbumin sensitization. Histologic sections showed severe granulomatous inflammatory cell infiltrates in all compartments of the lung, including peribronchial, perivascular, and alveolar spaces. The mRNA levels of proinflammatory cytokines interleukin-1beta and tumor necrosis factor {alpha} and the chemokine CCL3/MIP-1{alpha} were also markedly increased in the lungs. Despite the enhancement of the pulmonary inflammatory reaction, exposure to S. chartarum spores significantly down-regulated airway hyperresponsiveness and showed a tendency to decrease levels of Th2 cytokines in the lung.

Conclusion: Exposure to S. chartarum modulates the inflammatory reaction and airway hyperresponsiveness, depending on the allergic status of the exposed mice.

Key Words: allergy • asthma • experimental model • mold




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