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Am J Physiol Lung Cell Mol Physiol 274: L66-L71, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 1, L66-L71, January 1998

Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung

Timothy S. Brannon1, Amy N. MacRitchie1, Marina A. Jaramillo2, Todd S. Sherman1, Ivan S. Yuhanna1, Linda R. Margraf2, and Philip W. Shaul1

Departments of 1 Pediatrics and 2 Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9063

Prostacyclin is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in whole lung increases during that period. The rate-limiting enzyme in prostacyclin synthesis in the developing lung is cyclooxygenase (COX). We investigated the ontogeny and cellular localization of COX-1 (constitutive) and COX-2 (inducible) gene expression in lungs from late-gestation fetal lambs, 1-wk-old newborn lambs (NB1), and 1- to 4-mo-old newborn lambs (NB2). COX-1 mRNA abundance rose progressively from fetal to NB1 to NB2, increasing 12-fold overall. In parallel, immunoblot analysis revealed a progressive increase in COX-1 protein, rising fourfold from fetal lambs to NB2. COX-2 mRNA levels increased fivefold from fetal to NB1 but were similar in NB1 and NB2. However, COX-2 protein was not detectable by immunoblot analysis in any age group. Immunohistochemistry for COX-1 showed intense immunostaining in endothelial cells at all ages. COX-1 was also expressed in airway epithelium at all ages, with a greater number of epithelial cells staining positively in NB2 compared with fetal and NB1 groups. In addition, COX-1 was expressed in airway smooth muscle from NB1. COX-2 immunostaining was absent in all age groups. These findings indicate that there is differential expression of COX-1 and COX-2 in the developing lung and that the enzymes are expressed in a cell-specific manner. The developmental upregulation in COX-1 may optimize the capacity for prostaglandin-mediated vasodilation, bronchodilation, and surfactant synthesis in the newborn lung.

airway epithelium; airway smooth muscle; immunohistochemistry; prostacyclin; vascular endothelium


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