RT Journal Article
SR Electronic
T1 Expression of plasminogen activator inhibitors type-1 and type-2 in the mouse lung after administration of crystalline silica
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 912
OP 921
DO 10.1183/09031936.98.11040912
VO 11
IS 4
A1 C Lardot
A1 M Heusterpreute
A1 P Mertens
A1 M Philippe
A1 D Lison
YR 1998
UL http://erj.ersjournals.com/content/11/4/912.abstract
AB Altered expression of plasminogen activator inhibitors (PAIs) is of potential relevance to the process of lung fibrosis. To clarify the involvement of PAIs in interstitial lung diseases, we examined whether alterations in PAI-1 and PAI-2 were induced in response to a single intratracheal administration of a fibrosing dose of crystalline silica in mice (5 mg x animal(-1)). The time course of changes in PAI activity and PAI-1 protein were characterized in bronchoalveolar lavage fluid (BALF) and changes in PAI-1 and PAI-2 messenger ribonucleic acid (mRNAs) were monitored by reverse transcriptase polymerase chain reaction (RT-PCR) in BALF cells and lung tissue up to the fibrotic stage of the disease. Substantial levels of PAI activity were found in BALF of control animals, whereas no PAI-1 protein was detected. In response to silica treatment, we observed an acute increase of PAI activity and PAI-1 protein levels in BALF (day 1), associated with an induction of PAI-1 and PAI-2 mRNA levels in lung tissue. In alveolar macrophages, silica treatment induced a persistent upregulation of PAI-2 mRNA only. One month after silica treatment, PAI activity was undetectable in BALF while substantial PAI activity was still present in controls. At the same time point, sustained upregulation of PAI-1 and PAI- 2 mRNAs was, however, noted in lung tissue of animals treated with silica. These findings support the possible implication of PAIs in the remodelling process induced by silica in the lung.