Abstract
It has been suggested that prior exposure to mineral dust may attenuate the ability of the alveolar macrophage (AM) to respond to subsequent provocative stimuli, thus compromising the host defense mechanism. On the contrary, prior exposure of the AM with lipopolysacharride (LPS) has been shown to sensitize the AM for subsequent stimuli, thereby enhancing the reactivity of the AM. Since AM-derived eicosanoids serve as important mediators of the lung's response to AM activation, we evaluated the relative effects of LPS and silica dust on the production of several key eicosanoids when these activating agents were administered in sequence. Prior exposure of AM to LPS, followed by exposure to silica dust, led to an enhanced production of thromboxane A2 (TXA2) and leukotriene B4 (LTB4) when results were compared to AM stimulated with silica alone. In contrast, prior exposure of AM to silica dust reduced the ability of AM to respond to LPS, since levels of PGE2 and TXA2 produced by silica-primed AM subsequently exposed to LPS were lower than those produced by AM exposed to LPS alone. The results of these studies suggest that underlying bacterial infection in the lung may exacerbate the inflammatory effects of silica dust, while chronic occupational exposure to silica may reduce the ability of the AM to respond to bacterial invasion of the lung.