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Published ahead of print on February 1, 2007, doi:10.1165/rcmb.2006-0234OC

Am. J. Respir. Cell Mol. Biol., Volume 36, Number 6, June 2007, 669-677

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Submitted on June 29, 2006
Revised on January 30, 2007

Dendritic Cells and Macrophages Form a Transepithelial Network Against Foreign Particulate Antigens

Fabian Blank1*, Barbara Rothen-Rutishauser1, and Peter Gehr1

1 Division of Histology, Institute of Anatomy, University of Bern, Bern, Switzerland

* To whom correspondence should be addressed. E-mail: fabian.blank{at}ana.unibe.ch.

Fine particles (0.1-2.5µm in diameter) may cause increased pulmonary morbidity and mortality. We demonstrate with a cell culture model of the human epithelial airway wall that dendritic cells extend processes between epithelial cells through the tight junctions to collect particles in the "luminal space" and to transport them through cytoplasmic processes between epithelial cells across the epithelium or to transmigrate through the epithelium to take up particles on the epithelial surface. Furthermore dendritic cells interacted with particle loaded macrophages on top of the epithelium and with other dendritic cells within or beneath the epithelium to take over particles. By comparing the cellular interplay of dendritic cells and macrophages across epithelial monolayers of different transepithelial electrical resistance we found that more dendritic cells were involved in particle uptake in A549 cultures showing a low transepithelial electrical resistance compared to dendritic cells in16HBE14o cultures showing a high transepithelial electrical resistance 10min (23.9% vs. 9.5%) and 4h (42.1% vs. 14.6%) after particle exposition. In contrast the macrophages in A549 co-cultures showed a significant lower involvement in particle uptake compared to 16HBE14o co-cultures 10min (12.8% vs. 42.8%) and 4h (57.4% vs. 82.7%) after particle exposition. Hence we postulate that the epithelial integrity influences the particle uptake by dendritic cells and that these two cell types collaborate as sentinels against foreign particulate antigen by building a transepithelial interacting cellular network.




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