Pulmonary cyclooxygenase-1 (COX-1) and COX-2 cellular expression and distribution after respiratory syncytial virus and parainfluenza virus infection

Abstract

Prostaglandins (PGs) play an important role in pulmonary physiology and various pathophysiological processes following infection. The initial step in the biosynthesis of PGs is regulated by two distinct cyclooxygenase enzymes, cyclooxygenase-1 (COX-1) and COX-2. The goal of this study was to investigate the pulmonary cellular localization and distribution of COX-1 and COX-2 in a neonatal lamb model following respiratory syncytial virus (RSV) and parainfluenza virus 3 (PI3) infection, organisms that also cause significant respiratory disease in children. No significant differences were seen in pulmonary COX-1 expression at various microanatomical locations following RSV or PI3 infection compared to controls. In contrast, COX-2 was upregulated following RSV and PI3 infection. Strong expression was restricted to bronchial and bronchiolar epithelial cells and macrophages, while minimal expression was present in the same microanatomical locations in the uninfected lungs. Other microanatomical locations in both the controls and the infected lungs lacked expression. This work suggests that during RSV or PI3 infection: (1) COX-1 cellular expression is not altered, (2) COX-2 cellular expression is upregulated in airway bronchiolar and bronchial epithelial cells and macrophages, (3) respiratory epithelium along with macrophages are important microanatomical compartments regulating the host inflammatory response during viral infection, and (4) COX-2 may be a potential target for RSV and PI3 therapy.

FIG. 1.

(A) COX-1 expression in the lung from a control lamb. Strong (++++) expression in bronchial smooth muscle cells (long arrows) and macrophages (arrowheads) can be seen (immunohistochemical stain, original magnification 10 ×). (B) COX-1 expression in the lung from a RSV-infected lamb. Strong (++++) expression in bronchial smooth muscle cells (long arrows), alveolar septa (short arrows), and vascular endothelial cells (arrowheads) can be seen (immunohistochemical stain, original magnification 10 ×). (C) COX-1 expression in the lung from a PI3-infected lamb. Strong (++++) expression in bronchial and bronchiolar smooth muscle cells (long arrows) and vascular endothelial cells (arrowheads) can be seen (immunohistochemical stain, original magnification 10 ×).

FIG. 1.

(A) COX-1 expression in the lung from a control lamb. Strong (++++) expression in bronchial smooth muscle cells (long arrows) and macrophages (arrowheads) can be seen (immunohistochemical stain, original magnification 10 ×). (B) COX-1 expression in the lung from a RSV-infected lamb. Strong (++++) expression in bronchial smooth muscle cells (long arrows), alveolar septa (short arrows), and vascular endothelial cells (arrowheads) can be seen (immunohistochemical stain, original magnification 10 ×). (C) COX-1 expression in the lung from a PI3-infected lamb. Strong (++++) expression in bronchial and bronchiolar smooth muscle cells (long arrows) and vascular endothelial cells (arrowheads) can be seen (immunohistochemical stain, original magnification 10 ×).

FIG. 2.

(A) COX-2 expression in the lung from a control lamb. Minimal (+) expression in bronchial and bronchiolar epithelial cells (long arrows) can be seen (immunohistochemical stain, original magnification 10 ×). (B) COX-2 expression in the lung from an RSV-infected lamb. Strong (++++) expression in bronchiolar epithelial cells (long arrows) and macrophages (short arrows) can be seen (immunohistochemical stain, original magnification 10 ×). (C) COX-2 expression in the lung from a PI3-infected lamb. Strong (++++) expression in bronchial epithelial cells (long arrows) and macrophages (short arrows) can be seen (immunohistochemical stain, original magnification 10 ×).

FIG. 2.

(A) COX-2 expression in the lung from a control lamb. Minimal (+) expression in bronchial and bronchiolar epithelial cells (long arrows) can be seen (immunohistochemical stain, original magnification 10 ×). (B) COX-2 expression in the lung from an RSV-infected lamb. Strong (++++) expression in bronchiolar epithelial cells (long arrows) and macrophages (short arrows) can be seen (immunohistochemical stain, original magnification 10 ×). (C) COX-2 expression in the lung from a PI3-infected lamb. Strong (++++) expression in bronchial epithelial cells (long arrows) and macrophages (short arrows) can be seen (immunohistochemical stain, original magnification 10 ×).