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Am J Respir Crit Care Med. 2007 Nov 1;176(9):892-901. Epub 2007 Aug 9.

Lung dendritic cells elicited by Fms-like tyrosine 3-kinase ligand amplify the lung inflammatory response to lipopolysaccharide.

Author information

1
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Giessen Lung Center, Giessen, Germany.

Abstract

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-alpha 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.

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.

PMID:
17690334
DOI:
10.1164/rccm.200608-1068OC
[Indexed for MEDLINE]

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