Oxygen toxicity is attributed to the reaction of oxygen metabolites with cellular components leading to cell destruction. Activation of latent human neutrophil interstitial collagenase by reactive oxygen species has been demonstrated. The potential role of collagenases in hyperoxic lung injury has not been investigated. We studied the effect of hyperoxia on newborn rat lung water content, morphology and ultrastructure, interstitial (type I) and type IV collagenase gene expression and type I and IV collagenolytic activity. We observed that hyperoxia causes pulmonary edema, alters newborn rat lung morphology in a sequential manner and produces ultrastructural alterations, induces type I and increases type IV collagenase mRNA expression, and increases type I and IV collagenolytic activity. A role for type I and IV collagenase in hyperoxic newborn lung injury or in the recovery following the injury is proposed.
The extracellular matrix is important in the cellular differentiation and morphogenesis of the lung. The basement membrane (BM), an integral part of the extracellular matrix, is composed primarily of type IV collagen. The metabolism of type IV collagenase is important in remodeling of BM that occurs during growth. We examined the ontogeny of rat lung type IV collagenase mRNA expression, type IV collagenolytic activity and type IV collagen content during the perinatal period. In addition, the effect of prenatal glucocorticoid (GC) treatment on fetal lung type IV collagenase mRNA expression and type IV collagenolytic activity was studied. Lung polyadenylated RNA was extracted and subjected to Northern blot analysis and laser densitometry after hybridization with human type IV collagenase (∼72 kD) and rat actin cDNA probe. Type IV collagenolytic activity and type IV collagen concentration were quantitated by an enzymatic and a radioimmunoassay, respectively. While lung type IV collagenase mRNA to α-actin ratio and type IV collagenolytic activity were highest prior to birth (21-day fetus), the lung type IV collagen concentration was lowest at this time. Prenatal GC treatment did not influence type IV collagenase mRNA expression or the collagenolytic activity. A role for fetal lung type IV collagenase in preparation for the neonatal pulmonary vascular and/or alveolar adaption is proposed.
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