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Endotoxin Augments Myeloid Dendritic Cell Influx into the Airways in Patients with Allergic Asthma

¹ Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), Hannover, Germany; and ² Center for Environmental Medicine, Asthma, and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Correspondence and requests for reprints should be addressed to Norbert Krug, M.D., Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany. E-mail: norbert.krug{at}item.fraunhofer.de

Rationale: Epidemiologic studies have shown that exacerbation of asthma is modulated by environmental endotoxin. High levels of endotoxin are associated with asthma symptoms and the current use of asthma medication. However, the underlying mechanisms by which endotoxin modulates asthma are not completely understood.

Objectives: The aim of the study was to test whether endotoxin enhances the response of individuals with allergic asthma to allergen, and to determine if this interaction is associated with increased numbers of antigen-presenting cells in the airways.

Methods: Seventeen subjects with mild allergic asthma underwent segmental challenge with allergen, endotoxin, and the combination of both in three different lung segments via bronchoscopy. The cellular influx including monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), as well as the level of cytokines, were assessed in bronchoalveolar lavage fluid obtained 24 hours after segmental challenge. Monocytes, mDCs, and pDCs were isolated and their capacity to induce T cell proliferation was determined.

Measurements and Main Results: Endotoxin enhanced the cellular response to allergen. The combination of allergen and endotoxin resulted in increased numbers of total cells, lymphocytes, neutrophils, eosinophils, monocytes, and mDCs, as well as increased levels of lipopolysaccharide-binding protein, IL-1, IL-6, and tumor necrosis factor– in the bronchoalveolar lavage fluid compared with allergen alone. Isolated mDCs but not pDCs induced a strong T cell proliferation in vitro.

Conclusions: Endotoxin augments the allergic inflammation in the lungs of individuals with asthma, and induces an enhanced influx of monocytes and functionally active antigen-presenting mDCs into the respiratory tract.

Key Words: dendritic cells • monocytes • bronchoalveolar lavage • endobronchial allergen challenge • mixed lymphocyte culture test

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Epidemiologic studies have linked exacerbations of asthma to environmental endotoxin and animal studies, suggesting that myeloid dendritic cells play a key role in inducing and maintaining an adaptive immune response to lung allergens. What This Study Adds to the Field We have shown in individuals with allergic asthma that endotoxin augments allergen-dependent allergic airway inflammation and enhances airway influx of myeloid dendritic cells. These data suggest a mechanism by which endotoxin increases asthma severity.