L. Ermert et al., Rat pulmonary cyclooxygenase-2 expression in response to endotoxin challenge - Differential regulation in the various types of cells in the lung, AM J PATH, 156(4), 2000, pp. 1275-1287
Citations number
61
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Cyclooxygenase (Cox), the key enzyme of prostanoid synthesis, consists of t
he two isoforms Cox-1 and Cox-2, both recently noted to be constitutively e
xpressed in rat lungs with a distinct profile of cellular distribution. The
responsiveness of pulmonary Cox-1 and Cox-2 expression to intravascular en
dotoxin lipopolysaccharide (LPS) administration was investigated in isolate
d, ventilated rat lungs, buffer-perfused with or without admixture of rat p
lasma. Immunohistochemical staining intensity was measured by a previously
described method of silver enhancement and epipolarization image analysis,
Both the Cox-1 mRNA, quantified in the whole lung homogenate, and the cellu
lar localization of Cox-1 were unchanged in response to LPS, In contrast, t
ime- and dose-dependent up-regulation of Cox-2 mRNA (lung homogenate) occur
red, and differential LPS reactivity at the cellular level was observed. Up
-regulation of Cox-2 in cell types expressing this enzyme already under bas
eline conditions was noted in bronchial epithelial cells, bronchial and vas
cular smooth muscle cells, cells within the BALT and myocytes of the large
hilar veins. De novo induction of Cox-2 occurred in endothelial cells and t
he majority of alveolar macrophages. Down-regulation of Cox-2 was observed
in perivascular and peribronchial macrophage-like cells. Moreover, differen
tial impact of plasma components was noted: for the large majority of cells
, CD14 surface expression correlated with Cox-2 responsiveness to LPS indep
endent of plasma, whereas the presence of plasma components was a prerequis
ite for the LPS response in CD14-negative cells. LPS did not provoke physio
logical changes in the perfused lungs, but markedly enhanced baseline prost
anoid generation. We conclude that LPS-induced Cox-2 regulation occurs in a
complex, cell-specific manner, which may be relevant for pathogenetic sequ
elae in septic lung injury and acute respiratory failure.