Collagen Synthesis during Lung Development and during Hyaline Membrane Disease in the Nonhuman Primate

Abstract

To assess maturational changes in collagen synthesis, lung tissue was obtained from healthy Macaca nemestrina monkeys at different ages, ranging from 68% of term gestation to adulthood. We hypothesized that infants delivered prematurely have a greater rate of collagen synthesis than do older animals because of their greater rate of lung growth during gestation. Secondly, we hypothesized that lung repair in infants with hyaline membrane disease (HMD) is associated with an additional increase in lung collagen synthesis rate. Therefore, lung tissue was obtained during the first week of life from monkeys delivered at 82% of term gestation, a stage at which half of them developed HMD. The rate of total protein synthesis in lung samples was determined by measuring the incorporation of [3H]proline; the rate of collagen synthesis was determined by measuring the conversion of proline into hydroxyproline. Premature monkeys had a higher rate of collagen synthesis (9.9 +/- 2.7 nmol/mg DNA/h) than did term infants (5.3 +/- 1.1) or older animals (2.1 +/- 0.4, p less than 0.05). There was no additional increase in rate of collagen synthesis in animals with HMD from 3 h (14.3 +/- 6.9) to 7 days of age (15.1 +/- 6.1); control premature animals also had no significant change during the first week of life (10.9 +/- 3.0 at 3 h; 11.6 +/- 4.6 at 7 days). The early stage of recovery from HMD in premature monkeys does not appear to be associated with an increase in collagen production beyond the already increased synthesis rate associated with lung growth.

Prenatal inflammation enhances antenatal corticosteroid–induced fetal lung maturation

“…Suppression of collagen and other extracellular matrix genes represent a large proportion of suppressed signature genes for matrix fibroblasts after LPS exposure. While the total lung collagen content increases with lung growth and maturation, the synthesis rate of collagen decreases from 80% gestation to full term (35,42). Collagen is responsible for the lung structure, but it does not contribute to the lung compliance and elasticity, which is provided by the elastic fibers -mainly elastin and microfibrils (43).…”

Full-Tidal Liquid Ventilation with Perfluorocarbon for Prevention of Lung Injury in Newborn Non-Human Primates

“…Studies in liquid ventilation have required high proximal airway pressures; experiments in newborn lambs demonstrated that in one protocol the use of peak airwav pressure equal to 31.5 torr was associated with peak alveolar pressure of only 18.6 torr due to a large flow resistive pressure drop of 13 torr along the bronchial tree[12]. Previously in our laboratories, we have studied the impact of conventional and high frequency ventilation on the development of lung injury in prematurelydelivered monkeys[3,32]. Previously in our laboratories, we have studied the impact of conventional and high frequency ventilation on the development of lung injury in prematurelydelivered monkeys[3,32].…”

Four decades of leading‐edge research in the reproductive and developmental sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

“…The composition of pulmonary surfactant and how it changes with fetal maturity and postnatally with HMD was studied [Jackson et al, 1986, 1988]. The pulmonary inflammatory response to preterm delivery and mechanical ventilation was studied [Jackson et al, 1988, 1987] along with lung repair mechanisms [Jackson et al, 1990a,b]. Prenatal steroids were found to accelerate pulmonary development and surfactant production with an increase in lung compliance [Kessler et al, 1982, Truog et al, 1983].…”