You are here:
MODULATION OF EICOSANOID PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES EXPOSED TO SILICA IN VITRO
Citation:
Koren, H., M. Joyce, R. Devlin, S. Becker, K. Driscoll, AND M. Madden. MODULATION OF EICOSANOID PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES EXPOSED TO SILICA IN VITRO. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/D-90/196 (NTIS PB91136630).
Description:
Repeated inhalation of silica dust can lead to inflammation and fibrosis in human lung and in experimental animal models. he alveolar macrophage is believed to play a pivotal role in this process. umerous macrophage-derived growth factors, cytokines and arachidonic acid metabolites have been shown to contribute to inflammation and fibrosis. he objective of this study was to determine the eicosanoid production by human alveolar macrophages in response to silica exposure in vitro and to assess their contribution to silica-induced fibrosis and inflammation. Macrophages were obtained from healthy volunteers and were incubated for 3 or 24 hours in the presence of silica (100, 60, and 0 ug/ml). upernatants were removed for eicosanoid analysis. icosanoids were analyzed by both HPLC and RIA. he data suggested that silica caused an increased release of LTB4, LTC4/D4/E4, and 5-HETE after 3 hours; and decreases in PGE2 and TXB2 production after 24 hours exposure to 100ug/ml silica. n 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. he pattern of eicosanoid production after exposure to silica was different from that obtained when macrophages were stimulated with LPS for 3 or 24 hrs, indicating that the response to the particles was not just due to general cellular activation.