Alveolar type II cells, surfactant protein A (SP-A), and the phospholipid components of surfactant in acute silicosis in the rat.

Silica instillation causes a massive accumulation of surfactant phospholipids and the appearance of hypertrophic type II cells in the rat. We have examined the metabolic consequences of silica instillation with a special emphasis on surfactant protein A (SP-A), the major glycoprotein of surfactant. Fourteen days after instillation of 10 mg of silica, the amount of phospholipids in lavage increased 14-fold and the amount of SP-A increased 10-fold. The phospholipid composition of lavage material from silica-treated animals was altered by a reduction in the percentage of phosphatidylglycerol and an increase in phosphatidylinositol. The percentage of saturated phosphatidylcholine did not change. Type II cells isolated from rats treated with silica could be separated into cells of normal size and of increased size by centrifugal elutriation. There was an increase in phospholipid and SP-A content in the larger type II cells isolated from silica-treated rats relative to type II cells from control rats (by 45% and 70%, respectively, when expressed per micrograms protein; p less than 0.01). Activities of the phospholipid biosynthetic enzymes cholinephosphate cytidyltransferase, lysophosphatidylcholine acyltransferase, and phosphatidylglycerol phosphate synthetase increased (nmol/min/mg cell protein) in the hypertrophic type II cells relative to type II cells from control rats (by 40%, 112%, and 95%, respectively, p less than 0.05). Incorporation of (1-14C)-acetate was also increased in hypertrophic type II cells relative to type II cells from control rats (by 43%, p less than 0.05). The only difference in the distribution of acetate incorporated into individual lipids was a slight increase in the percentage incorporated into phosphatidylinositol. Although the increase in phosphatidylcholine found in the lavage could be due to increased synthesis as reflected by the changes in enzymatic activity and rate of acetate incorporation, the reduction in phosphatidylglycerol in lavage and in type II cells could not be explained simply by a reduction in synthesis on the basis of available data. There was a marked increase in SP-A content in lavage and in type II cells isolated from silica-treated rats without a significant change in the relative abundance of SP-A mRNA. This dissociation of SP-A mRNA abundance and apoprotein content suggests that factors other than transcription may be important for the observed accumulation of SP-A in silica-treated rats. We conclude that the phospholipidosis and proteinosis that occur subsequent to silica instillation in the rat lung are not solely attributable to increase in the rates of synthesis of these components.