Increased production of matrix metalloproteinase-2 in alveolar macrophages and regulation by interleukin-10 in patients with acute pulmonary sarcoidosis

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. The 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 by bronchoalveolar lavage and cultured without stimulation and in presence of tumor necrosis factor alpha (TNF alpha) and interleukin-10 (IL-10). The release of cathepsins and MMPs as well as IL-10 and TNF alpha was measured in the super natant 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 TNFa 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 alpha 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 alpha 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 AM of patients with sarcoidosis and the MMP downregulation by exogenous 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.