Experimental silicosis. II. Long-term effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs.

Rats received intratracheal instillations of 50 mg of silica (quartz, 0.5 mu particles). One, 2, 4, 5, 6, 9, and 12 months later, the lungs were evaluated histologically and by various biochemical measurements. The lung content of protein, proline, and hydroxyproline (collagen) were quantitated, as were the synthesis rates of lung collagen and the total lung protein (evaluated with lung minces in vitro. The ratio of newly synthesized and of total lung Type I to Type III collagen was also determined. These experiments were performed in parallel on rats free of chronic respiratory disease and a strain of conventional animals. The authors conclude that 1) the excess collagen deposited in granulomas and/or silicotic nodules as part of the fibrotic response of the lung is similar to normal lung collagen with respect to relative ratios of Types I and III present, in contrast to the response of the lung to oxidant pneumotoxins; 2) the response of the lung to silica continues for at least 1 year; 3) there are essentially no differences in the response of chronic respiratory disease-free Sprague-Dawley and conventional Wistar rats to intratracheally instilled silica. Both strains of rats develop silica-containing granulomas, mature silicotic nodules, and areas of alveolar lipoproteinosis associated with interstitial pneumonitis. Even 1 year after instillation of silica areas of granulomas, silicotic nodules and alveolar lipoproteinosis may be observed in most of the lungs studied; ie, these responses are not mutually exclusive.