Published ahead of print on August 9, 2007, doi:10.1164/rccm.200608-1068OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200608-1068OC
Lung Dendritic Cells Elicited by Fms-like Tyrosin 3-Kinase Ligand Amplify the Lung Inflammatory Response to Lipopolysaccharide1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Giessen Lung Center, Giessen, Germany; and 2 Department of Pulmonary Medicine, Hannover School of Medicine, Hannover, Germany Correspondence and requests for reprints should be addressed to Ulrich A. Maus, Ph.D., Hannover School of Medicine, Department of Pulmonary Medicine, Laboratory for Experimental Lung Research, Hannover 30625, Germany. E-mail: maus.ulrich{at}mh-hannover.de Rationale: Strategically located beneath the alveolar epithelial barrier, dendritic cells (DCs) of the lung are centrally involved in the sampling and processing of inhaled antigens. However, the contribution of DCs to acute lung inflammation induced by inhaled bacterial toxins is largely unknown. Objectives: To determine the effect of increased lung DC numbers elicited by Fms-like tyrosine kinase-3 ligand (Flt3L) on the acute lung inflammatory response to Escherichia coli lipopolysaccharide (LPS) and Klebsiella pneumoniae infection. Methods: Mice were pretreated with Flt3L either in the absence or presence of anti-CD11a antibodies to block the Flt3L-elicited lung DC accumulation or were made transiently neutropenic and then challenged with E. coli LPS or K. pneumoniae.
Measurements and Main Results: Flt3L-pretreated mice challenged with LPS responded with drastically increased numbers of both lung parenchymal and alveolar DCs together with an aggravated neutrophilic alveolitis, elevated tumor necrosis factor- Conclusions: Lung DCs actively participate in the early inflammatory response to both inhaled bacterial toxins and live bacteria and play a yet unrecognized role in regulating lung barrier integrity.
Key Words: dendritic cell • lung • inflammation • neutrophil • monocyte
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and IL-12 levels, and a strongly increased lung permeability compared with LPS- or Flt3L-only–treated mice. Anti–CD11a-mediated blockade of lung DC accumulation significantly attenuated the lung permeability developing in response to LPS, whereas transient neutropenia did not affect lung permeability changes. Finally, Flt3L-pretreated mice responded with increased lung permeability and decreased survival upon infection with K. pneumoniae. 
