The epithelial integrity is preserved during particle exchange across the epithelium by macrophages and dendritic cells

Abstract

The epithelium of the human airway wall serves as structural and functional barrier against inhaled and deposited particulate antigen. Recently we have shown that human blood monocyte-derived dendritic cells (MDDC) and human blood monocytes derived macrophages (MDM) collaborate as sentinels against foreign particulate antigen by building a transepithelial interacting cellular network. Although the tight junction belt was penetrated by processes of MDDC and MDM to transfer particles across the epithelium, the monolayer integrity of the epithelial cells was not affected. These results brought up two main questions: (1) How is the epithelial integrity preserved? (2) If MDM and MDDC make a direct contact by their processes can they exchange particles? The presence of tight junction and adherens junction mRNA and proteins in MDM and MDDC monocultures was determined by RT-PCR, and immunofluorescence. Living co-cultures of MDM and MDDC exposed to particles (1 mm in diameter) were investigated by laser scanning microscopy. We found that MDDC as well as MDM express adherens junction and tight junction mRNA and proteins as shown by RT-PCR and SDS-Page. Furthermore, performing live cell experiments we have seen that MDDC and MDM moved towards each other and that particles were transferred from MDM to MDDC. Interestingly, MDDC also made contacts with other MDDC and we observed particle exchange between them as well. We may conclude from these findings that MDM and MDDC can form tight junction and adherens junction-like structures with epithelial cells to preserve the epithelial integrity during particle translocation across the epithelium. In addition, we demonstrate an exchange of particles from MDM to MDDC and MDDC to MDDC which supports our hypothesis that MDM and MDDC collaborate as sentinels.