Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients

Abstract

Pulmonary emphysema is a condition of the lung characterised by progressive destruction Background -Matrix degradation in emand loss of functioning alveoli. The mechphysema has long been attributed to the anisms involved in extracellular matrix (ECM) action of neutrophil elastase (NE). More damage are not precisely known but a sigrecently a role for other proteases, parnificant body of evidence supports the proteaseticularly the matrix metalloproteinases antiprotease theory which postulates that an (MMPs), in the pathogenesis of this disexcess of proteolytic activity over the inhibitory ease has been proposed. To date, however, capacity of the lung leads to parenchymal dethe presence of MMPs in the lungs of struction. 1 Most studies to date have focused patients with emphysema has not been on the role of neutrophil elastase (NE) as the demonstrated.major effector protease involved. 2 More reMethods -Samples of bronchoalveolar cently, however, there has been considerable lavage (BAL) fluid from 10 patients with speculation on the potential involvement of emphysema and from control subjects other proteases, particularly the matrix metallomatched for sex and current smoking proteinases (MMPs), in matrix degradation in status were assessed for collagenase, emphysema.3 gelatinase, and NE activity. PulmonaryThe MMPs are a highly homologous family function tests and computed tomographic of endopeptidases which are collectively cap-(CT) scans were carried out on all study able of breaking down all the constituents of subjects.the alveolar ECM, including collagen, elastin, Results -Collagenase activity was detected proteoglycans, laminin, and fibronectin.4 They in BAL fluid samples from all em-are produced by a range of stromal cells and physematous patients but in only one by two of the major inflammatory cells imsmoking control (p<0.001). Gelatinase B plicated in emphysema -the alveolar macrowas present in six patients and in two phage and the neutrophil. Indirect evidence smoking controls (p<0.03). The con-that MMPs may play a part in tissue destruction comitant presence of gelatinase B in in emphysema comes from a number of studies. complex with lipocalin (NGAL) in the gel-Janoff et al demonstrated that the elastolytic atinase positive samples suggests that the activity of bronchoalveolar lavage (BAL) fluid neutrophil is a significant source of the from smokers was significantly inhibited by gelatinase B observed. NE was detected in metal chelating agents and concluded that

Markers of emphysema are associated with more severe chronic obstructive pulmonary disease

“…An increase in BAL concentrations and macrophage expression of MMP-9 (gelatinase B) has been reported in patients with emphysema as compared to normal volunteers. [28][29] Our results, obtained by a noninvasive method, such as sputum induction, extend this finding. Indeed, MMP-9 levels and MMP-9/TIMP-1 ratio were higher in COPD patients with emphysema than in both controls and COPD patients without emphysema, thus suggesting an amplified protease imbalance in the emphysema phenotype of COPD.…”

Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space

“…According to previous studies on local quantity and/or activity of MMP-9 and MMP-2 in human airways, gelatinases are increased in COPD and emphysema patients compared with nonsmokers [4,15] and chronic smokers without COPD [3,16], while the latter do not display significantly different MMP-9 protein levels in relation to never-smokers [17]. Notably, a recent study on smokers with and without COPD reveals that immunoreactivity for MMP-2 protein in peripheral lung tissue correlates with disease severity in patients with COPD rather than to cigarette smoking per se [18], which is fully in line with the current findings.…”

“…Thus, an upregulation of MMP-9 and MMP-2 has been demonstrated in the lungs of patients with manifest chronic obstructive pulmonary disease (COPD), and an upregulation of MMP-9 has been detected in the lungs of patients with emphysema [3]. This upregulation of MMP may lead to an imbalance in the gelatinase homeostasis, especially if occurring in combination with a downregulation of TIMPs [4,5].…”

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

“…Increased levels of MMP-1 and MMP-9 have been detected in bronchoalveolar lavage fluid of patients with emphysema (Finlay et al, 1997b). As compared with healthy subjects, patients with COPD have a marked increase in expression and activity of MMP-2, MMP-9 and MT1-MMP in their lung parenchyma (Ohnishi et al, 1998) and increased gelatinolytic activity linked to MMP-2 and MMP-9 in their sputum (Cataldo et al, 2000;Vignola et al, 1998b).…”