Modification of matrix metalloproteinase activites from alveolar macrophages during chronic coal mine dust exposure in rats
Résumé
Macrophage derived products have been implicated in pneumoconiosis induced by chronic coal dust inhalation. To assess the role of macrophages during chronic inflammatory processes in relation to pneumoconiosis, we investigated their capacity to secrete matrix metalloproteinase (MMP) activities, which are largely involved in the degradation and the remodelling of extracellular matrix components. Two groups of rats (N = 48 per group) were exposed to 100 or 200 mg m-3,6 h per day, 5 days per week and sacrified at 9,28 and 78 days of exposure, and 6 months following the end of exposure. A total of 92 kDa proform and 88 kDa active form collagenase type IV (gelatinase) were investigated by enzymography in macrophage culture medium (MEM), macrophage extracts (MACs) and bronchoalveolar fluid (BAL). In parallel, net gelatinase and interstitial collagenase activities were evaluated by degradation of radiolabelled specific substrates. Pneumoconiotic lesions progressively developed during the late dust exposure and the recovery phase, and were associated with macrophage alveolitis. Results clearly showed that, at each step of chronic dust exposure as well as during the recovery phase, chronic coal dust inhalation induced the increase of total gelatinase activities secreted into the MEM and the BAL. The net gelatinase and collagenase activities were increased in parallel in MEM whereas, they appeared inhibited when secreted in the BAL whatever the dust exposure time. These results suggest that chronic coal mine dust exposure is capable of inducing chronic alveolar MACs activation in regard to their persistant highly increased capacity to degrade in situ extracellular matrix components, namely collagen types IV or V [HIBBS et al, J. din. Invest. 80,1644-1650 (1987)]. Such a dysregulation associated with the acute inhibition process towards MMPs in the alveolar space, allowed us to propose a role of MMPs during pneumoconiosis.