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

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

Correspondence and requests for reprints should be addressed to Fabian Blank, Institute of Anatomy, Division of Histology, University of Bern, Baltzerstrasse 2, CH-3000 Bern 9, Switzerland. E-mail: fabian.blank{at}ana.unibe.ch

Fine particles (0.1–2.5 µm 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 with dendritic cells in16HBE14o cultures showing a high transepithelial electrical resistance 10 min (23.9% versus 9.5%) and 4 h (42.1% versus 14.6%) after particle exposition. In contrast, the macrophages in A549 co-cultures showed a significantly lower involvement in particle uptake compared with 16HBE14o co-cultures 10 min (12.8% versus 42.8%) and 4 h (57.4% versus 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.

Key Words: dendritic cells • airway macrophages • cellular interplay • particle translocation • confocal laser scanning microscopy

CLINICAL RELEVANCE The mechanisms of particle uptake by immune cells of the airway wall shown in our study, and in particular the profound involvement of the highly competent antigen-presenting dendritic cells, constitute important new knowledge of the defense mechanism of the lung.

 

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