Am. J. Respir. Cell Mol. Biol., Volume 18, Number 4, April, 1998 479-488

Cyclooxygenase Isoenzyme Localization and mRNA Expression in Rat Lungs

L. Ermert, M. Ermert, M. Goppelt-Struebe, D. Walmrath, F. Grimminger, W. Steudel, H. A. Ghofrani, C. Homberger, H.-R. Duncker, and W. Seeger

Department of Pathology, Department of Internal Medicine, and Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Giessen, Germany; Research Laboratories of Nephrology, Department of Internal Medicine IV, University Erlangen-Nürnberg, Erlangen, Germany; and Department of Anesthesia, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts

Prostanoid generation may proceed via both isoforms of cyclooxygenase, Cox-1 and Cox-2. Cox-1 is thought to be ubiquitously expressed, whereas Cox-2 is mostly assumed to be dynamically regulated, responding to inflammatory stimuli. The cellular localization of Cox-1 and Cox-2 in the lung, an organ with high cyclooxygenase activity, is not known. In normal rat lungs the expression and localization of Cox-1 and Cox-2 were examined with immunogold-silver staining and the RT-PCR technique. Quantitative image analysis of the staining intensity was performed by measuring mean gray values of digitized epipolarization images. Expression of both Cox-1 and Cox-2 was readily detectable in rat lungs. Cox-1 immunoreactivity localized predominantly to bronchial epithelial cells, smooth muscle cells of large hilum veins, and (with lower expression) to alveolar macrophages and pulmonary artery endothelial cells. The most intense Cox-2 staining was noted in macrophage- and mast cell-like cells, detected in close vicinity to the bronchial epithelium and in the connective tissue surrounding the vessels. In addition, strong Cox-2 expression was found in smooth muscle cells of partially muscular vessels and large veins of the hilum. Bronchial epithelial cells displayed Cox-2 immunoreactivity with limited intensity. Alveolar macrophages and alveolar septal cells were only occasionally stained with anti-Cox-2 antibodies. Both Cox-1 and Cox-2 are constitutively expressed in several cell types of normal rat lung, but display clearly different patterns of cellular localization. Cox-2 may not be related only to lung inflammation, but is suggested to be implicated in regulatory processes under physiological conditions as well.

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