ENHANCED RELEASE OF PROSTAGLANDIN-E(2) FROM MACROPHAGES OF RATS WITH SILICOSIS

The pathogenesis of silicosis results, in part, from interactions betw een silica particles and alveolar macrophages (AM) with release of cyt okines and other mediators. Different arachidonic acid metabolites hav e been shown to promote or to suppress inflammation and fibrosis. We d esigned experiments to study the production of cyclooxygenase metaboli tes and tumor necrosis factor-alpha (TNF-alpha) from macrophages durin g active silicosis. Macrophages were harvested from rats 5 to 7 mo aft er an 8-day silica aerosol exposure. Upon in vitro culture of AM, the spontaneous release of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and prostaglandin D2 (PGD2) of silica-exposed animals was higher than that of sham-exposed animals. Moreover, AM from silicotic rats displa yed an increased sensitivity to low concentrations of lipopolysacchari de (LPS, 10 ng/ml) and released copious amounts of PGE2 and TXB2. When compared with similarly enhanced release of TNF-alpha from AM of sili ca-exposed rats, PGE2 production occurred later and started to increas e when TNF-alpha production declined. Addition of the cyclooxygenase b locker indomethacin augmented TNF-alpha production, whereas the additi on of PGE2 counteracted TNF-alpha release. Also peritoneal macrophages , which did not have direct contact with silica particles, released en hanced levels of PGE2 in response to low LPS doses. We conclude that A M and other macrophages from silica-exposed rats are preactivated and display an enhanced prostanoid production that could serve anti-inflam matory or immunomodulating roles in silicosis.