Cigarette smoking induces an elastolytic cysteine proteinase in macrophages distinct from cathepsin L

Reilly, John J.; Chen, P.; Sailor, L. Z.; Wilcox, David K.; Mason, Robert W.; Chapman, Harold A.

doi:10.1152/ajplung.1991.261.2.l41

Cited by 17 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activity is reported to be elevated in BAL fluid as well as lysates of BAL cells from smokers [12], but other reports have suggested that the activity attributed to cysteine proteinases in BAL cell lysates may be due not only to cathepsin L but also to other cysteine proteinases [29]. As cathepsins S and K were recently discovered and reported to have an elastolytic activity, this may explain such undetermined activities in BAL cell lysates and/or in BAL fluid itself.…”

Section: Discussionmentioning

confidence: 95%

Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema

Takeyabu¹,

Betsuyaku²,

Nishimura³

et al. 1998

Eur Respir J

View full text Add to dashboard Cite

aaProtease-antiprotease imbalance theory has been a central theme for the last 30 years in the study of the pathogenesis of pulmonary emphysema [1,2]. Although smoking is a major exogenous cause of pulmonary emphysema, only a small percentage of smokers develop clinically apparent pulmonary emphysema. Numerous studies have examined the effect of cigarette smoking on the proteaseantiprotease balance in body fluids, but few have focused on individual differences in the susceptibility to pulmonary emphysema. Most studies have simply compared smokers and nonsmokers [3,4] or healthy subjects and patients with chronic obstructive pulmonary disease (COPD), mostly clinically diagnosed through pulmonary function tests [5]. However, the data from subjects with established COPD could be influenced by possible concomitant infections of the respiratory tract.It was previously demonstrated that neutrophil elastase (NE) complexed with α 1 -protease inhibitor (α 1 -PI; NE-α 1 -PI complex) in bronchoalveolar lavage (BAL) fluid was significantly increased in community-based older volunteers who had subclinical emphysema, as evidenced by lung computed tomographic (CT) scans, compared with those who had a comparable smoking history but no evidence of emphysema [6]. In addition, the releasability of NE from alveolar macrophages (AM) was shown to be high in those subjects with emphysema [7]. FINLAY et al. [8] recently reported that the levels of collagenase and gelatinase B in BAL fluid from subjects with clinically apparent emphysema were significantly higher than in healthy subjects.Another important class of proteases which is a candidate for causing chronic pulmonary destruction consists of the cysteine proteases, one of which, cathepsin L, has potent elastolytic activity at acidic pH [9,10] and is capable of inactivating α 1 -PI catalytically [11]. The expression of cathepsin L messenger ribonucleic acid (mRNA), as well as the activity of cathepsin L, was reported to be higher in BAL cells from smokers than in nonsmokers [12]. It is also possible that chronic smoking may decrease the level of cystatin C, an inhibitor of cathepsin L in the lungs, so that emphysematous changes are more likely to occur [13]. However, to our knowledge, there have been no reports on the levels of cathepsin L and cystatin C in BAL fluid from subjects with subclinical emphysema.In this study, the activities and immunological quantities of cathepsin L and cystatin C in BAL fluid from asymptomatic community-based older volunteers were evaluated and the releasability of cathepsin L from AM was examined in vitro. Cathepsin B was also measured in BAL fluid, which has little elastolytic activity. In particular, the Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. K. Takeyabu, T. Betsuyaku, M. Nishimura, A. Yoshioka, M. Tanino, K. Miyamoto, Y. Kawakami. ©ERS Journals Ltd 1998. ABSTRACT: This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in com...

show abstract

Section: Discussionmentioning

confidence: 95%

Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema

Takeyabu¹,

Betsuyaku²,

Nishimura³

et al. 1998

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Cigarette smoke and other irritants stimulate alveolar macrophages to produce MMPs [33,34] and cathepsins [35]. MMP1 degrades collagen whereas MMP9, MMP12, CTSL and CTSS degrade elastin [36].…”

Section: Discussionmentioning

confidence: 99%

Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema

et al. 2013

View full text Add to dashboard Cite

Alveolar macrophages play an important role in chronic obstructive pulmonary disease via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes.Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed.The results showed that basal expression level of MMP12 mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/ alveolar volume and was positively related to the extent of emphysema. The basal expression of MMP1 mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted.We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation. @ERSpublications MMP12 expression may play a role in the pathogenesis of emphysema and airflow limitation

show abstract

“…Cathepsins B, L, and S all work at acidic pH and their proteolytic activity is neutralized at neutral pH with the exception of cathepsin S (12). Cathepsin L activity has been shown to be elevated in bronchoalveolar lavage (BAL) fluid from emphysema (13) and the release of cathepsin B and S from macrophages has been induced by cigarette smoking (14,15). Indeed, cathepsin L has been shown to cleave and inactivate ␣ 1 -antitrypsin (16), the major serine protease inhibitor present in the lung (17).…”

Section: Secretory Leucoprotease Inhibitor (Slpi)mentioning

confidence: 99%

Cathepsin B, L, and S Cleave and Inactivate Secretory Leucoprotease Inhibitor

Taggart

Lowe

Greene

et al. 2001

Journal of Biological Chemistry

174

158

View full text Add to dashboard Cite

Cigarette smoking induces an elastolytic cysteine proteinase in macrophages distinct from cathepsin L

Cited by 17 publications

References 0 publications

Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema

Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema

Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema

Cathepsin B, L, and S Cleave and Inactivate Secretory Leucoprotease Inhibitor

Contact Info

Product

Resources

About