Effects of silica on the composition of the pulmonary extracellular lining.

The effects of intratracheally injected silica on lung weights and on alveolar macrophages, polymorphonuclear leukocytes, phospholipid, protein, N-acetyl-beta-glucosaminidase, and alkaline phosphatase of the extracellular lining of rat lungs were studied as functions of dose and time. All of these parameters increased with time up to 12 days after a single injection of silica (200 mg/kg) and showed a dose dependence in their responses. Extracellular soluble protein increased 19.8-fold from 1.9 to 37.6 mg/pair of lungs. The composition of the extracellular soluble protein was very similar to that found in normal lungs as determined with two-dimensional-polyacrylamide gel electrophoresis. Although most of the soluble proteins in lavage effluents were similar to those found in serum, several serum proteins were absent, indicating that the selectivity of the lungs for certain serum proteins was maintained after treatment with silica. Increases in extracellular soluble proteins could not be accounted for by damage to the blood/air barrier. Extracellular phospholipid increased 12.1-fold from 1.74 to 21.1 mg/pair of lungs. The phosphatidylcholine content of this phospholipid resembled that of normal pulmonary surfactant but was different from that in free cells lavaged from the lungs of control and silica-treated rats. Increases in extracellular phospholipid were probably due to silica effects on the surfactant system and not to destruction of or release by free cells in the alveoli. N-Acetyl-beta-glucosaminidase and alkaline phosphatase increased approximately 33- and 6-fold, respectively, in response to silica. The number of alveolar macrophages and polymorphonuclear leukocytes increased 1.5- and 75-fold, respectively. Calculation of partial correlations revealed statistically significant relationships among extracellular phospholipids, soluble proteins, and the two hydrolytic enzymes, suggesting that these components were being released into the lung lining from a common source or by a common mechanism.