title: Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases.
abstract: Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure to asbestos caused rat AM to exhibit high production of transforming growth factor-beta (TGF-β) with prolonged survival in the absence of other cells, not simultaneously with the apoptosis caused by asbestos. The NK cell line showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, and primary NK cells in culture with asbestos and peripheral blood NK cells in mesothelioma shared a decrease in expression of NKp46, a representative activating receptor. The AM finding indicates that AM contribute to asbestosis by playing a direct role in the fibrogenic response, as well as the inflammatory response. The response of NK cells indicates that exposure to asbestos has an immune-suppressive effect, as well as a tumorigenic effect. Our studies therefore reveal novel effects of asbestos exposure on AM and tumor immunity, which may represent valuable information for construction of a strategy for prevention and cure of asbestosis and malignant mesothelioma.
authors: Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. yas@med.kawasaki-m.ac.jp
authors: Yasumitsu
authors: Y
authors: Nishimura
authors: Megumi
authors: M
authors: Maeda
authors: Naoko
authors: N
authors: Kumagai-Takei
authors: Suni
authors: S
authors: Lee
authors: Hidenori
authors: H
authors: Matsuzaki
authors: Yasuhiko
authors: Y
authors: Wada
authors: Tamako
authors: T
authors: Nishiike-Wada
authors: Hiroshi
authors: H
authors: Iguchi
authors: Takemi
authors: T
authors: Otsuki
mesh_terms: D000818:Animals; D001194:Asbestos / Q000276:immunology / Q000633:toxicity*; D001195:Asbestosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004785:Environmental Pollutants / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008175:Lung Neoplasms / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008654:Mesothelioma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D051381:Rats
chemical_list: D004785:Environmental Pollutants; D001194:Asbestos