title: Lung macrophage-epithelial cell interactions amplify particle-mediated cytokine release.
abstract: Interactions between alveolar macrophages (AMs) and epithelial cells may promote inflammatory responses to air pollution particles. Normal rat AMs, the alveolar type II epithelial cell line RLE-6TN (RLE), or cocultures of both cell types were incubated with various particles (0-50 microg/ml) for 24 h, followed by assay of released TNF-alpha and MIP-2. The particles used included titanium dioxide (TiO2), alpha-quartz (SiO2), residual oil fly ash (ROFA), or urban air particles (UAP). For all particles, a dose-dependent increase in TNF-alpha and MIP-2 release was observed in AM+RLE co-cultures but not in RLE or AM monoculture. AM+RLE co-culture also synergistically enhanced basal levels of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2. In contrast, when AMs were co-cultured with fibroblasts, basal and particle-induced TNF-alpha and MIP-2 were similar to levels found in AM monoculture. Particle uptake by AMs was similar in mono- or AM+RLE co-culture. Increased basal and particle-induced cytokine release were not observed when the AMs were physically separated from the RLE. This contact-dependent cytokine potentiation could not be blocked with anti-CD18/anti-CD54, arginine-glycine-aspartate (RGD) peptide, or heparin. We conclude that in vitro inflammatory responses to particles are amplified by contact-dependent interactions between AMs and epithelial cells. AM-epithelial co-culture may provide a useful model of in vivo particle effects.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ftao@hpsh.harvard.edu
authors.forename: Florence
authors.initials: F
authors.lastname: Tao
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D015815:Cell Adhesion Molecules; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D014025:Titanium