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Published ahead of print on April 3, 2008, doi:10.1164/rccm.200706-870OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 12, June 2008, 1307-1313

A more recent version of this article appeared on June 15, 2008
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Submitted on June 15, 2007
Accepted on April 3, 2008

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

Frank Schaumann1, Meike Muller1, Armin Braun1, Birgit Luettig1, David B Peden2, Jens M Hohlfeld1, and Norbert Krug1*

1 Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), Hannover, Germany, 2 Center for Environmental Medicine, Asthma, and Lung Biology, UNC School of Medicine, UNC Chapel Hill, Chapel Hill, NC, USA

* To whom correspondence should be addressed. E-mail: norbert.krug{at}item.fraunhofer.de.

Rationale: Epidemiological 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 is not completely understood. Objectives: The aim of the study was to test whether endotoxin enhances the response of allergic asthmatics 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 BAL 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 LPS-binding protein, IL-{alpha}, IL-6, and TNF-{alpha} in the BAL fluid compared to allergen alone. Isolated mDCs but not pDCs induced a strong T-cell proliferation in vitro. Conclusion: Endotoxin augments the allergic inflammation in the lung of asthmatics 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







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