Patients with confirmed interstitial pneumonia were initially classified histologically into "desquamative" (n = 40) and "usual" (n = 53) types, and followed for one to 22 years. Both the diagnosis and the extent of fibrosis affected the course and response to therapy. Mortality in desquamative interstitial pneumonia was 27.5 per cent, and mean survival 12.2 years, as compared with 66.0 per cent and 5.6 years in usual interstitial pneumonia (P less than 0.01). Without treatment, 21.9 per cent with the desquamative but none with the usual type improved. With corticosteroid therapy, 61.5 per cent with desquamative and only 11.5 per cent with usual interstitial pneumonia improved, whereas 27.0 per cent and 69.2 per cent worsened. We conclude that the histologic classification of chronic interstitial pneumonia used here permits forecasts of prognosis and response to treatment that cannot be deduced from other data.
The aim of this study was to examine the hypothesis that alveolar macrophages represent a significant source of matrix-degrading proteinases in the emphysematous lung. Macrophages from bronchoalveolar lavage fluid of 10 patients with emphysema and 10 normal volunteers were maintained in vitro for 24 h and assessed semiquantitatively for mRNA transcript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase. Release of these MMPs into the culture medium and secretion of neutrophil elastaselike activity was also assessed. Elevated levels of mRNA transcripts for gelatinase B (p < 0.0005) and interstitial collagenase (p < 0.0005) were observed in macrophages from emphysematous patients. Increased collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were also measured in conditioned medium from patient macrophages. With gelatinase B, complexed forms of the enzyme were secreted by patient but not by control macrophages. No difference in transcript levels of gelatinase A or MME was observed between patient and control samples, and neither enzyme was detected in macrophage-conditioned media from either group. These results directly demonstrate that alveolar macrophages from the emphysematous lung produce elevated quantities of matrix-degrading enzymes with both elastolytic and collagenolytic activities.
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
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