ALTERATIONS IN EICOSANOID PRODUCTION BY RAT ALVEOLAR TYPE-II CELLS ISOLATED AFTER SILICA-INDUCED LUNG INJURY

Although alveolar type II cells in primary culture have been shown to produce eicosanoids and exposure of type II cells to silica in vitro alters eicosanoid production, the production of eicosanoids by alveolar type II cells isolated after acute lung injury in vivo has not been evaluated. Therefore, we investigated the production of arachidonic acid (AA) metabolites by alveolar type II cells isolated after silica-induced lung injury. Alveolar type II cells were isolated from rats 14 days after intratracheal silica instillation and from untreated animals. Type II cells were separated into normotrophic and hypertrophic populations by centrifugal elutriation, and secreted eicosanoids were determined under basal and stimulated conditions by enzyme immunoassay on the day of isolation and after 1 day in culture. Under basal conditions, freshly isolated type II cells from silica-treated animals produced more prostaglandin (PG) E2 than 6-keto-PGF1-alpha or thromboxane B2 (TxB2). Production of all three prostanoids increased with increasing cell size. The calcium ionophore A23187 stimulated a less than 2-fold increase in PGE2 and 6-keto-PGF1-alpha production in all groups of cells. In contrast, this calcium ionophore greatly enhanced TxB2 and leukotriene C4 (LTC4) production by normotrophic type II cells from both untreated and silica-treated animals. Incubation with exogenous AA suggested that the increased capability of the hypertrophic cells to synthesize PGE2 and TxB2 was due primarily to an increase in arachidonate availability. The hypertrophic type II cells also appear to have increased prostacyclin synthase activity. There were no differences in the catabolism of PGE2 between the normotrophic and the hypertrophic type II cells. After 1 day in culture, the cell size differences in PGE2 and TxB2 production between the normotrophic and hypertrophic type II cells isolated from silica-treated animals were no longer present. We conclude that the metabolism of AA by isolated type II cells is altered by in vivo silica-induced lung injury and that hypertrophic and normotrophic type II cells isolated from silica-treated animals have distinct eicosanoid production profiles that distinguish these populations of type II cells from each other and from type II cells isolated from untreated animals. Increased basal production of PGE2 and PGI2 by freshly isolated hypertrophic type II cells suggests that these cells may play a reparative role in the resolution of lung injury.