TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Hoppstädter, Jessica A1 - Diesel, Britta A1 - Zarbock, Robert A1 - Breinig, Tanja A1 - Monz, Dominik A1 - Koch, Marcus A1 - Meyerhans, Andreas A1 - Gortner, Ludwig A1 - Lehr, Claus-Michael A1 - Huwer, Hanno A1 - Kiemer, Alexandra K. T1 - Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages JF - Respiratory Research N2 - Background: Investigations on pulmonary macrophages (MF) mostly focus on alveolar MF (AM) as a well-defined cell population. Characteristics of MF in the interstitium, referred to as lung interstitial MF (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods: Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results: IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MF populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion: AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MF in the inflammatory response. KW - dendritic cells KW - gene-expression KW - flow-cytometry KW - DNA KW - monocytes KW - lipopolysaccharide KW - identifaiction KW - mycobacteria KW - IL-10 KW - methylation Y1 - 2010 UN - https://nbn-resolving.org/urn:nbn:de:bsz:291:415-3665 SN - 1465-9921 SS - 1465-9921 U6 - https://doi.org/10.1186/1465-9921-11-124 DO - https://doi.org/10.1186/1465-9921-11-124 VL - 11 IS - 9 SP - 124 S1 - 124 ER -