title: Modulation of eicosanoid production by human alveolar macrophages exposed to silica in vitro.
abstract: Repeated inhalation of silica dust can lead to inflammation and fibrosis in human lung and in experimental animal models. The alveolar macrophage is believed to play a pivotal role in this process. Numerous macrophage-derived growth factors, cytokines, and arachidonic acid metabolites have been shown to contribute to inflammation and fibrosis. The objective of this study was to determine the eicosanoid production by human alveolar macrophages in response to silica exposure in vitro and to assess the contribution of alveolar macrophages to silica-induced fibrosis and inflammation. Macrophages were obtained from healthy volunteers and were incubated for 3 or 24 hr in the presence of silica (100, 60, and 0 micrograms/mL). Supernatants were removed for eicosanoid analysis. Eicosanoids were analyzed by both high performance liquid chromatography and radioimmunoassay. The data suggest that silica causes an increased release of leukotriene B4, leukotrienes C4/D4/E4, and 5-hydroxyeicosatetraenoic acid (5-HETE) after 3 hr and decreases in prostaglandin E2 and thromboxane B2 production after 24 hr of exposure to 100 micrograms/mL silica. In addition, 12-HETE and 15-HETE production remained unchanged at either time point. These opposing effects seen with the metabolites of lipoxygenase and cyclooxygenase pathways could contribute to silica-induced fibrosis. The pattern of eicosanoid production after exposure to silica was different from that obtained when macrophages were stimulated with lipopolysaccharide for 3 or 24 hr, indicating that the response to the particles was not just due to general cellular activation.
authors.affiliation: Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
authors.forename: H S
authors.initials: HS
authors.lastname: Koren
authors.forename: M
authors.initials: M
authors.lastname: Joyce
authors.forename: R B
authors.initials: RB
authors.lastname: Devlin
authors.forename: S
authors.initials: S
authors.lastname: Becker
authors.forename: K
authors.initials: K
authors.lastname: Driscoll
authors.forename: M C
authors.initials: MC
authors.lastname: Madden
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D015777:Eicosanoids; D015289:Leukotrienes; D016718:Arachidonic Acid; D012822:Silicon Dioxide