Collagen crosslinking in lungs of rats with experimental silicosis

Rats were intratracheally instilled with 50 mg of size-fractionated crystalline quartz to induce silicosis. Lungs were analyzed 1, 4, 6, and 9 months after instillation for their content of the reduced difunctional collagen crosslinks dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL), of the nonreducible trifunctional (mature) crosslink, hydroxypyridinium (OHP), and of hydroxylysine. Ratios of DHLNL: HLNL were elevated in silicotic lung collagen at all times sampled, due both to increased levels of DHLNL and decreased amounts of HLNL. Hydroxylysine content of collagen in the silicotic lungs was also increased as compared with age-matched control rats. Hydroxypyridinium content of silicotic lung collagen was less than control values at 1 month, but was significantly increased to about 120%, 150%, and 175% of the age-matched control values at 4, 6, and 9 months after silica instillation, respectively. The increased levels of OHP in lung collagen were temporally correlated with the appearance of mature silicotic nodules in these lungs. We conclude that the large amounts of excess collagen deposited in silicotic lungs differs biochemically from normal lung collagen despite maintenance of the normal ratio of major collagen types in silicotic lungs.