The balance of lung connective tissue elements in elastase-induced emphysema

Elastase-induced emphysema is associated with changes in all components of connective tissue, including elastin. The abnormal restructuring of lung parenchyma that occurs after elastase administration in hamsters might reflect an abnormal balance of elastin, collagen, and glycosaminoglycan in lung parenchyma. To test this hypothesis, we measured total amounts and levels of accumulation over 24 hr of connective tissue elements in lung explants at several points over a 1-year period after a single elastase treatment in hamsters. We found acute, early changes in the metabolism of elastin, collagen, and glycosaminoglycan consistent with degradation of elastin and increased turnover of collagen and glycosaminoglycan. By day 21 after elastase treatment, lung elastin had returned to control values, then rose and stayed elevated throughout the remainder of the study period. Total collagen levels rose in both control and elastase-treated lungs by the same amount over the year period. However, incorporation of 14C-proline into collagen hydroxyproline was elevated only in elastase-treated lungs over the period of 21 to 360 days. Incorporation of 14C-glucosamine into glycosaminoglycan was greatest over the period of 1 to 5 days after treatment and total levels also peaked at this time. By day 21 both incorporation of glucosamine and total levels of glycosaminoglycan had returned to normal, where they remained. The ratios of glycosaminoglycan to elastin and glycosaminoglycan to collagen were calculated over the period of 21 to 360 days to determine whether the long-term relative balance of these components had changed in elastase-treated lungs. We found that a steady-state imbalance existed between heparan sulfate and collagen and heparan sulfate and elastin, suggesting that an inappropriate amount of heparan sulfate was present relative to the amounts of collagen and elastin. We conclude that administration of elastase results in changes in the long-term balance of lung connective tissue components.