Characteristic Elevation of Matrix Metalloproteinase Activity in Idiopathic Interstitial Pneumonias

Abstract

Destruction of subepithelial basement membrane is a key event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To evaluate the role of matrix metalloproteinases (MMPs) in parenchymal remodeling in idiopathic interstitial pneumonia (IIP), we studied MMP-2 and -9 activity, in bronchoalveolar lavage fluid (BALF) by zymography and the expression of MMP-2 and -9 and TIMP-2 in lung tissue by immunohistochemistry. BALF and lung tissues were collected from 26 patients with usual interstitial pneumonia (IPF-UIP), 11 with nonspecific interstitial pneumonia (NSIP), and 6 with bronchiolitis obliterans organizing pneumonia (BOOP). IPF-UIP cases showed predominant expression of MMP-9, whereas NSIP and BOOP cases showed predominant MMP-2 expression in BALF and in tissues. In BALF samples from rapidly progressive IPF-UIP cases, neutrophil-derived MMP-9 activity, as well as MMP-9 active form were characteristically detected. Furthermore, the MMP-9 activity correlated significantly with an increase of neutrophils in BALF, whereas the MMP-2 activity associated with NSIP and BOOP correlated with an increase of lymphocytes. These results indicate that MMP-9 in IPF-UIP and MMP-2 in NSIP and BOOP may contribute to pulmonary structural remodeling through type IV collagenolytic activity. The characteristic contributions of matrix-degrading proteins may relate to the distinct prognostic features of these diseases.

Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis

“…been implicated in this disease process. 40 Using a similar experimental approach to that of the present study, Zuo et al 11 demonstrated enhanced expression of MMP-7 (matrilysin) mRNA in the lungs of patients with IPF and showed that that genetic deficiency of MMP-7 in mice conferred protection against bleomycin-induced pulmonary fibrosis. Thus, although the precise mechanism or mechanisms by which MMPs are involved in pulmonary fibrosis remain to be clarified, these studies provide support for the notion that MMPs play a crucial role in the pathobiology of IPF.…”

The Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Idiopathic Interstitisal Pneumonia

“…When immunohistochemistry was considered, the main locus of the MMP-2 was fibroblasts composed of interstitial tissues. In previous reports, the concentration of MMP-2 in the fibrotic tissues was found to be correlated with the degree of progression of pulmonary fibrosis [6] [12], which is consistent with the results of our study. Conversely, MMP-9 was observed in the neutrophils and lymphocytes of patients with IIP.…”

Interfering with extracellular matrix degradation to blunt inflammation

“…MMP's -1, 2, 8 and 9 have also been demonstrated to be elevated in asthmatic airways albeit to a lesser extent than in COPD [20]. Increased expression of MMPs-8, 9 and 7 has been demonstrated in the fibrosing diseases, IPF and pulmonary sarcoidosis [21][22][23][24].…”