Effect of surfactant on basal and silica-induced eicosanoid production by the alveolar macrophage.
Inflammation 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) LTB4 may be the most important eicosanoid mediator of the long-term effects of silica dust exposure on lung pathophysiology.
Kuhn
D C
DC
Department of Pathology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.
Demers
L M
LM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology*; D000818:Animals; D001688:Biological Products; D004305:Dose-Response Relationship, Drug; D004391:Dust; D015777:Eicosanoids / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011663:Pulmonary Surfactants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013997:Time Factors
D001688:Biological Products; D004391:Dust; D015777:Eicosanoids; D011663:Pulmonary Surfactants; D007975:Leukotriene B4; D015060:1,2-Dipalmitoylphosphatidylcholine; D013928:Thromboxane A2; D012822:Silicon Dioxide; C072197:beractant