Effect of Surfactant on Basal and Silica-Induced Eicosanoid Production by the Alveolar Macrophage

"Kuhn, Douglas C., and Laurence M. Demers. Effect of surfactant on basal and silica-induced eicosanoid production by the alveolar macrophage. Am. J . Physiol. 269 (Lung Cell. Mol. Physiol. 13): L165-Ll 70, 1995.-Infiammation and fibrosis subsequent to the inhalation of certain mineral dust particles has been suggested to result from the activation of eicosanoid synthesis by the alveolar macrophage (AM). To determine if surfactant modifies dust-induced generation of eicosanoids by the AM, we evaluated the effect of the surfactant lipid dipalmitoyl lecithin (DPL) on the production of eicosanoids by rat AM exposed to respirable silica dust in vitro. During the first 24-h exposure period, DPL alone significantly increased basal production of eicosanoids but completely inhibited silica-induced thromboxane A2 synthesis. In contrast, leukotriene B4 (LTB4 ) production was only partially reduced by DPL. During a second 24-h exposure period, LTB4 production in response to the highest dose of silica remained significantly elevated in the presence of DPL. Similar results were obtained when the surfactant preparation Survanta was evaluated. These results suggest that 1 ) DPL and Survanta independently activate AM eicosanoid production, 2) DPL and Survanta modulate the response of the AM to silica dust, and 3) L TB4 may be the most important eicosanoid mediator of the long-term effects of silica dust exposure on lung pathophysiology. THE OXYGENATED METABOLITES of arachidonic acid (AA) (here collectively termed eicosanoids) have been implicated as important regulators of lung physiology and are thought to be involved in pathophysiological sequelae such as acute respiratory distress syndrome, asthma, and the pulmonary complications of sepsis (20). This role is manifested through both direct effects on lung physiology as well as through an indirect modulatory effect on the release of other mediators of lung injury, in particular profibrotic cytokines such as the interleukins and tumor necrosis factor (15). Recently, exaggerated eicosanoid production by both the alveolar macrophage (AM) and the type II epithelial cell has been demonstrated to result from the exposure of these cells to several particulates, including crystalline silica (quartz) dust (5, 9, 17). These observations have led to the suggestion that eicosanoids play a major role in the etiology of pneumoconioses.Another secretory component of the pulmonary environment, surfactant, has been shown to modulate crucial AM functions, such as bactericidal activity and the recruitment of circulating immune cells (25). Indeed, an important feature of the lung's reaction to inhaled mineral dust is an increase in surfactant production, perhaps as a compensatory or protective response (1, 16). In addition, the alteration of the surface properties of mineral dust by surfactant or its components has been shown to influence the biochemical response of the AM to the dust, perhaps by altering the surface charge of the dust particle (11, 29, 32). And recently, Wallace et al. (28) have shown that the coating of mineral dust with surfactant, and its subsequent removal by lysosomal phospholipase, unmasks differences in dust cytotoxicity that are not apparent when AM are exposed to uncoated dust. Thus it appears that the inclusion of surfactant in in vitro exposure studies may be important in evaluating both the absolute levels of eicosanoid production by the normal and dust-exposed AM and the temporal relationship between dust exposure and the production of inflammatory mediators by the AM. Therefore, we characterized the effects of the surfactants dipalmitoyl lecithin (DPL; the primary lipid component of natural surfactant) and Survanta (a commercially available surfactant derived from bovine lung) on basal and silica-induced AM eicosanoid production during two 24-h periods after exposure to dust particles to both allow the enzymatic removal of surfactant from the particle surface and evaluate the k"