title: Responses of well-differentiated nasal epithelial cells exposed to particles: role of the epithelium in airway inflammation.
abstract: Numerous epidemiological studies support the contention that ambient air pollution particles can adversely affect human health. To explain the acute inflammatory process in airways exposed to particles, a number of in vitro studies have been performed on cells grown submerged on plastic and poorly differentiated, and on cell lines, the physiology of which is somewhat different from that of well-differentiated cells. In order to obtain results using a model system in which epithelial cells are similar to those of the human airway in vivo, apical membranes of well-differentiated human nasal epithelial (HNE) cells cultured in an air-liquid interface (ALI) were exposed for 24 h to diesel exhaust particles (DEP) and Paris urban air particles (PM(2.5)). DEP and PM(2.5) (10-80 microg/cm(2)) stimulated both IL-8 and amphiregulin (ligand of EGFR) secretion exclusively towards the basal compartment. In contrast, there was no IL-1beta secretion and only weak non-reproducible secretion of TNF-alpha. IL-6 and GM-CSF were consistently stimulated towards the apical compartment and only when cells were exposed to PM(2.5). ICAM-1 protein expression on cell surfaces remained low after particle exposure, although it increased after TNF-alpha treatment. Internalization of particles, which is believed to initiate oxidative stress and proinflammatory cytokine expression, was restricted to small nanoparticles (< or =40 nm). Production of reactive oxygen species (ROS) was detected, and DEP were more efficient than PM(2.5). Collectively, our results suggest that airway epithelial cells exposed to particles augment the local inflammatory response in the lung but cannot alone initiate a systemic inflammatory response.
authors.affiliation: Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris 7, 75251 Paris cedex 05, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Auger
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gendron
authors.forename: Christophe
authors.initials: C
authors.lastname: Chamot
authors.forename: Francelyne
authors.initials: F
authors.lastname: Marano
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Dazy
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D066258:Amphiregulin; D002460:Cell Line; D016207:Cytokines; D066255:EGF Family of Proteins; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D001335:Vehicle Emissions / Q000009:adverse effects*
chemical_list: C587848:AREG protein, human; D000393:Air Pollutants; D066258:Amphiregulin; D016207:Cytokines; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D018799:Intercellular Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase