Glycosaminoglycan synthesis in amiodarone-induced pulmonary fibrosis

Glycosaminoglycans (GAG) have previously been demonstrated to be synthesized in greater than normal amounts following a single intratracheal insufflation of bleomycin in hamsters. This suggests that GAG may play a role in the propagation of pulmonary fibrotic reactions. To further test this hypothesis, GAG synthesis was studied in a new hamster model of interstitial lung injury, induced by the cardiac drug, aminodarone. Animals received a single intratracheal instillation of 1.25 mg aminodarone. At 4, 9, and 21 days post-insufflation, the animals were sacrificed, their lungs removed, and 1 mm fragments placed in explant culture for 6 hours at 370C in the presence of 35S-sulfate. The labeled GAG were isolated and measured for 35S incorporation. The author then isolated the hexosamine portions of the respective GAGs, Heparan Sulfate (HEP S), Chondroitin-6-Sulfate (Ch-6-S) and Chondroitin-4-Sulfate and Dermatan Sulfate (CH-4-S and DS) using the enzyme ABC and paper chromatography. They also studied the GAG content and distribution in hamster lung fibroblasts incorporated with 35S for 48 hours and subjected to either 0, 0.01 mg, 0.1 mg, or 1 mg of aminodarone. GAG synthesis is increased at an early stage following the induction of lung injury by aminodarone and remains elevated for a 3 week period. The change in GAG distribution boards elevated CH-4-S and DS may be characteristic of interstitial diseases in general. The GAGs that are synthesized by fibroblasts may be responsible for the increased CH-4-S and DS synthesis