Abstract
Matrix metalloproteinases (MMPs) and cathepsins have been implicated in the pathogenesis of several interstitial lung diseases by their effects on inflammatory processes and extracellular matrix remodelling. T he aim of this study was to investigate whether macrophage-derived MMPs and cathepsins are involved in the pathogenesis of sarcoidosis. Therefore the release of MMP-2, MMP-9, and cathepsins B and L from alveolar macrophages (AM)in active pulmonary sarcoidosis was studied and compared to normal controls and patients with pneumonia and fibrosis. Patients with sarcoidosis (n = 11), pulmonary fibrosis (n = 7), and pneumonia (n = 9) and normal controls (n = 10) were enrolled in the study. AM were obtained bybronchoalveolar lavage and cultured without stimulation and in presence of tumor necrosis factor alpha (TNF α) and interleukin-10 (IL-10). The release of cathepsins and MMPs as well as IL-10 and TNF α was measured in the supernatant of cultured AM by fluorimetric assays and zymography. AM of patients with sarcoidosis and pneumonia spontaneously released more MMP-2 than normal controls. Stimulation with TNF α showed no effects on MMP-2 and MMP-9 production. Exogenous IL-10 led partially to an inhibition of the MMP-2 and MMP-9 release. Patients with sarcoidosis produced significantly more IL-10 and TNF α than normal controls. This was not observed in patients with fibrosis and pneumonia. The spontaneous release of cathepsins B and L did not differ between the patient groups and normal controls and was not affected by TNF α and IL-10. The data show that AM of patients with sarcoidosis and pneumonia release significant amounts of MMP-2. The endogenous production of IL-10 in AMof patients with sarcoidosis and the MMP downregulation byexogenous IL-10 suggest an involvement of IL-10 in MMP regulation. Furthermore the results suggest that the production of MMP-2 is more specific for acute lung injury, rather than for a single lung disease such as sarcoidosis.