Comparison of In Vitro and In Vivo Rates of Collagen Synthesis in Normal and Damaged Lung Tissue

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Abstract
The rate of collagen synthesis was measured in vivo and in vitro in both normal and damaged mouse lung tissue. Acute lung damage was induced by the administration of butylated hydroxytoluene (BHT). The production of labeled hydroxyproline, following the administration of labeled proline, was used as an index of collagen production. Total and labeled hydroxyproline in normal and damaged lung tissue were solubilized equally following digestion with purified collagenase. Assuming that the extent of hydroxylation was not altered, this indicated that hydroxyproline was an accurate index of collagen content and production in damaged as well as normal lung tissue. The quantities of hydroxyproline formed at various times both in vivo and in vitro were calculated from the specific activity of free proline in lung tissue. The specific activity of free proline in normal and damaged lung tissue remained constant in vivo for at least 90 minutes after the intravenous injection of labeled proline. Hydroxyproline production was a linear function of time for up to 90 minutes in vivo and three hours in vitro. The in vivo rate of hydroxyproline production was significantly greater than the in vitro rate in lung tissue from similarly treated mice. The difference ranged from five-fold in normal lung tissue to eight-fold in lung tissue damaged by the administration of BHT. Comparable differences were seen between the in vivo and in vitro rates of non-collagen protein synthesis. Despite these differences in rates, the percentage of total protein synthesis committed to collagen in vivo was the same as in vitro in normal lung, and identical increases were seen in damaged lung. These data show that in vivo rates of both collagen and non-collagen protein synthesis are significantly higher than those measured in mouse lung tissue in vitro. Although the relative increases in collagen synthesis that occur in response to lung damage are larger in vivo, measurements of collagen synthesis in vitro do accurately reflect the general changes that accompany acute lung damage.