Cyclooxygenase Isoenzyme Localization and mRNA Expression in Rat Lungs

Abstract

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.

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

“…Similar findings were reported previously for rat and mouse pulmonary arteries (Ermert et al, 1998;Baber et al, 2005). A variety of other tissues have also been reported to express the COX-2 enzyme constitutively (O'Neill and Ford-Hutchinson, 1993;Watkins et al, 1999).…”

“…Of the COX isoforms identified, both COX-1 and COX-2 (Xie et al, 1991) were reported to be expressed constitutively in pulmonary vessels of the rat and mouse (Ermert et al, 1998;Baber et al, 2003Baber et al, , 2005. COX-1 is constitutively expressed in many tissues , whereas COX-2, often associated with inflammation, usually requires induction by cytokines (Hempel et al, 1994).…”

Cell-Specific Nitric Oxide Synthase-Isoenzyme Expression and Regulation in Response to Endotoxin in Intact Rat Lungs

“…In addition we report here bNOS expression for alveolar macrophages and VSMC of fully muscular vessels, as well as myocytes of hilar veins. Perivascular and peribronchial macrophage-like cells, which in previous studies were shown to represent mast cells to some major extent (Ermert et al, 1998(Ermert et al, , 2000b, were shown to express bNOS but not eNOS or iNOS in nonstimulated rat lung tissue.…”

Expression of cyclooxygenase‐1 and cyclooxygenase‐2 in bronchial epithelium and nonsmall cell lung carcinoma

“…Similarly, Cox 2 expression was not evident in normal rat bronchial epithelial cells according to animal studies in which polyclonal rabbit antimouse Cox 2 antibodies from either Cayman Chemical Co. 29 or Oxford Biomedical Research Inc. (Oxford, MI) 30 were used for immunostaining.…”

“…29 It is interesting to note that the normal rat lung tissues had no measurable Cox 2 expression. 29,30 This finding may explain why nonselective Cox inhibitors such as aspirin and sulindac suppress NNK-induced lung tumor-igenesis 15 whereas NS-398, a selective Cox 2 inhibitor, suppresses TPA-induced tumorigenesis in rats but not the TCDD-induced promotion of malignant transformation. 35 Therefore, it is possible that tobacco carcinogens may induce Cox 1 and Cox 2 expression through different mechanisms in the central bronchial epithelial cells and the peripheral airway, which may result in different carcinoma cell types.…”