EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITORS TYPE-1 AND TYPE-2 IN THE MOUSE LUNG AFTER ADMINISTRATION OF CRYSTALLINE SILICA

Altered expression of plasminogen activator inhibitors (PAIs) is of po tential relevance to the process of lung fibrosis, To clarify the invo lvement of PAIs in interstitial lung diseases, we examined whether alt erations in PAI-1 and PAI-2 were induced in response to a single intra tracheal administration of a fibrosing dose of crystalline silica in m ice (5 mg.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) we re monitored by reverse transcriptase polymerase chain reaction (RT-PC R) in BALF cells and lung tissue up to the fibrotic stage of the disea se, Substantial levels of PAI activity were found in BALF of control a nimals, whereas no PAI-1 protein was detected. In response to silica t reatment, we observed an acute increase of PAI activity and PAI-1 prot ein levels in BALF (day 1), associated with an induction of PAI-1 and PAI-2 mRNA levels in lung tissue. In alveolar macrophages, silica trea tment induced a persistent upregulation of PAI-2 mRNA only. One month after silica treatment, PAI activity was undetectable in BALF while su bstantial PAI activity was still present in controls. At the same time point, sustained upregulation of PAI-I and PAI-2 mRNAs was, however, noted in lung tissue of animals treated with silica. These findings su pport the possible implication of PAIs in the remodelling process indu ced by silica in the lung.