Leukotriene B4 and Tumor Necrosis Factor Production after invitro Exposure of Rat Alveolar Macrophages to Mineral Dust: Potential Role in Fibrogenesis
Prolonged inhalation of asbestos fibers and silica particles causes chronic inflammatory reactions and interstitial fibrosis. Although the exact mechanism by which these particles can induce lung diseases remains poorly understood, increasing evidence suggests that alveolar macrophages (AM) play a crucial role in the onset and development of asbestosis and silicosis through their ability to release potent inflammatory and fibrogenic mediators (Thomas and Hunninghake, 1987). Activated macrophages produce growth stimulatory activities toward fibroblasts and well characterized cytokines such as tumor necrosis factor (TNF) (Lemaire and al. 1986; Sayers and al. 1987). This cytokine, initially recognized because of its cytotoxic and anti-tumor properties, was shown in recent years to exert a role in systemic and lung inflammation (Moldawer and al. 1987; Bagby and Summer 1988), and in fibroblast growth regulation (Sugarman and al. 1985). Pulmonary macrophages also represent equally a particularly rich source of leukotriene B4 (LTB4). This lipoxygenase product may amplify the inflammatory process partly by its ability to modulate the production of immune and inflammatory cytokines, such as interleukin 1, interleukin 2 and gamma-interferon (Rola-Pleszczynski and Lemaire 1985; Rola-Pleszczynski and al. 1986). In this report, we investigated the role of LTB4 as a potential mediator of lung disease by examining the effect of endogenous and exogenous LTB4 on the regulation of mineral dust-induced INF release by rat AM. The contribution of TNF in macrophage-derived fibrogenic activity was also examined.
KeywordsAlveolar Macrophage Silica Particle Mineral Dust Asbestos Fiber Lipoxygenase Inhibitor
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