Intercellular communication between lung cells has been shown to modulate physiology and pathophysiology in the lung. In particular, it is apparent that the alveolar macrophage (AM) and the fibroblast (Fb) interact via soluble signaling molecules to mediate inflammation and fibrosis in response to a variety of noxious substances. To characterize the interaction of the AM and Fb in the relative production ofproin- flammatory eicosanoids in the lung, we evaluated basal and silica- activated production of prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and leukotriene B4 (LTB4) by human AM and Fb alone and when cultured together. Unstimulated AM and Fb cultured alone produced equal amounts of PGE2. However, AM produced 20-fold more TXA2 and 3-fold more LTB4than Fb. When AM and Fb were cultured together, either separated by a membrane or in physical contact with one another, the total production of TXA2 and LTB4 by both cell types was reduced by 70 to 90 percent while production of PGE2 was unaffected. When AM were first exposed to silica dust and then cocultured with Fb, the total production of PGE2 was decreased while that of TXA2 and LTB4 was unchanged compared to coculture in the absence of silica. The results of these studies suggest that basal eicosanoid synthesis may be modulated by the interaction of the AM and the Fb and that this communication is via soluble substances. In addition, dust-activated AM produce soluble mediators that may further alter lung eicosanoid production as part of a mechanism to modulate dust-induced pathophysiology.
All Science Journal Classification (ASJC) codes
- Public Health, Environmental and Occupational Health