ONTOGENY OF CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 GENE-EXPRESSION IN-OVINE LUNG

Prostacyclin is a key mediator of pulmonary vascular and parenchymal f unction during late fetal and early postnatal life, and its synthesis in whole lung increases during that period. The rate-limiting enzyme i n prostacyclin synthesis in the developing lung is cyclooxygenase (COX ). We investigated the ontogeny and cellular localization of COX-1 (co nstitutive) and COX-2 (inducible) gene expression in lungs from late-g estation fetal lambs, 1-wk-old newborn lambs (NB1), and 1- to 4-mo-old newborn lambs (NB2). COX-1 mRNA abundance rose progressively from fet al to NB1 to NB2, increasing 12-fold overall. In parallel, immunoblot analysis revealed a progressive increase in COX-1 protein, rising four fold from fetal lambs to NB2. COX-2 mRNA levels increased fivefold fro m fetal to NB1 but were similar in NB1 and NB2. However, COX-2 protein was not detectable by immunoblot analysis in any age group. Immunohis tochemistry for COX-1 showed intense immunostaining in endothelial cel ls at all ages. COX-1 was also expressed in airway epithelium at all a ges, with a greater number of epithelial cells staining positively in NB2 compared with fetal and NB1 groups. In addition, COX-1 was express ed in airway smooth muscle from NB1. COX-2 immunostaining was absent i n all age groups. These findings indicate that there is differential e xpression of COX-1 and COX-2 in the developing lung and that the enzym es are expressed in a cell-specific manner. The developmental upregula tion in COX-1 may optimize the capacity for prostaglandin-mediated vas odilation, bronchodilation, and surfactant synthesis in the newborn lu ng.