Cystatin C and Cathepsin B Production by Alveolar Macrophages From Smokers and Nonsmokers

Warfel, Alwin H.; Cardozo, Christopher; Yoo, Ok Hi; Zucker‐Franklin, Dorothea

doi:10.1002/jlb.49.1.41

Cited by 31 publications

(22 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increased level of cystatin C observed in the BALF of smokers with subclinical emphysema described by TAKEYABU et al [14] and data on the elevated cystatin C levels produced by alveolar macrophages from smokers [34] are in good agreement with this hypothesis regardless of the underlying disease process. Cathepsin D deposits detected in the extracellular matrix in injured tissue do not preclude the possibility of extracellular cathepsin activities in the micromilieu of matrix proteins [35].…”

Section: Discussionsupporting

confidence: 65%

Cathepsins in bleomycin-induced lung injury in rat

Koslowski¹,

Knoch²,

Kuhlisch³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

Cathepsins in bleomycin-induced lung injury in rat. R. Koslowski, K. Knoch, E. Kuhlisch, D. Seidel, M. Kasper. #ERS Journals Ltd 2003. ABSTRACT: Endogenous inhibitors tightly control the activity of proteinases in the extracellular space. Proteinase/antiproteinase imbalance may be caused by predominance of proteinases, resulting in severe tissue damage or abundance of proteinase inhibitors, leading to a shift in the balance of synthesis and degradation of extracellular matrix proteins and accumulation of these matrix components. Lung fibrosis is characterised by accumulation of fibrous matrix proteins in the alveolar interstitium.The activity of cathepsin D and amounts of cathepsins D and B in bleomycin-injured rat lung tissue and alveolar macrophages were examined. In addition, the activities of cathepsins and cysteine proteinase inhibitors (CPIs) in bronchoalveolar lavage fluid (BALF) were determined.No cathepsin but high CPI activity and large amounts of procathepsin B were detected in the BALF. In the alveolar lumen, the disturbed proteinase/antiproteinase balance for cysteine proteinases was clearly dominated by CPIs. In alveolar macrophages, the main source of increased cathepsin levels, large changes in cathepsin B and D content were observed during the inflammatory phase, corresponding to the occurrence of procathepsin B in BALF. With the end of the phase of tissue remodelling, imbalances in cathepsin and CPI activities were largely eliminated. Immunoblot data, revealing an increase in cathepsin D levels in myofibroblast-like cells compared to fibroblasts and in resting fibroblasts compared to proliferating cells, implicate this proteinase in the differentiation and conversion processes occurring at the beginning of the fibrotic phase of lung injury.The results show that cathepsin amounts and activities are increased transiently in lung tissue during regeneration processes in bleomycin-induced lung injury. Imbalances of cathepsin and cysteine proteinase inhibitors activities are also a phenomenon of the phase of tissue remodelling initiated by lung injury.

show abstract

Section: Discussionsupporting

confidence: 65%

Cathepsins in bleomycin-induced lung injury in rat

Koslowski¹,

Knoch²,

Kuhlisch³

et al. 2003

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…There have been two conflicting reports on the level of cystatin C in the culture medium of alveolar macrophages from smokers and nonsmokers. CHAPMAN et al [13] demonstrated that the level was lower in smokers than in nonsmokers, whereas WARFEL et al [30] reported the opposite findings. However, there have been no reports on the level of cystatin C in BAL fluid from subjects with emphysema.…”

Section: Discussionmentioning

confidence: 97%

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

“…It is a 14-kDa protein (120 amino acids) and is secreted by different cell types in vitro (27). Several proteinase inhibitors, such as thrombin inhibitors, calpain inhibitors, or cysteine protease inhibitors, have been suggested to be part of a regulatory system associated with neuronal differentiation.…”

Section: Discussionmentioning

confidence: 99%

A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells

Katô

Heike

Okawa

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Although embryonic stem (ES) cells are capable of unlimited proliferation and pluripotent differentiation, effective preparation of neural stem cells from ES cells are not achieved. Here, we have directly generated under the coculture with dissociated primary neurosphere cells in serum-free medium and the same effect was observed when ES cells were cultured with conditioned medium of primary neurosphere culture (CMPNC). ES-neural stem cells (NSCs) could proliferate for more than seven times and differentiate into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. The responsible molecule in CMPNC was confirmed by matrix-assisted laser desorption͞ionization time-of-flight mass spectrometry, which turned out to be cystatin C. Purified cystatin C in place of the CMPNC could generate ES-NSCs efficiently with self-renewal and multidifferentiation potentials. These results reveal the validity of cystatin C for generating NSCs from ES cells.coculture system ͉ conditioned medium of primary neurosphere culture N eurogenesis is considered to be the most complex event of organogenesis during embryonic development and involves a precise signaling, along with cellular interaction cascade, to generate the functional cellular networks. The embryonic organizer allows cells in its vicinity to execute their default neural program by emitting bone morphogenetic protein antagonists (1, 2). However, other works suggest a more complex mechanism (3-5).Neural stem cells (NSCs) are the self-renewal, multipotent cells that generate neurons, astrocytes, and oligodendrocytes (6, 7). They have great potential as a therapeutic tool for the repair of a number of central nervous system (CNS) disorders. Several in vitro systems allowing derivation of neuronal progeny from embryonic stem (ES) cells, which differentiate into all of the cell fates in a developing embryo, have been described. However, attempts to exclusively generate NSCs or neural progenitor cells from ES cells are restricted. It has been shown that neural fates emerge from ES cells in the serum-free conditions (8, 9). Although these procedures are noteworthy, both the quality and the quantity of ES-derived neural cells are not sufficient for further examination or clinical applications. Higher levels of neural differentiation are achieved by treatment of embryoid bodies with retinoic acid (RA) in the presence of FCS (10, 11) or by coculture with particular stromal cell lines (12, 13). The action of RA is pleiotropic (14, 15), whereas the effect of several stromal cell lines is attributed to an undefined neural inducing activity. These factors severely restrict the ability to use cells cultured with FCS or with particular stromal feeder cells for therapeutic treatments.Here, we developed an efficient system for the generation of ES cell-derived NSCs (ES-NSCs) during coculture with dissociated neurosphere cells without a need for FCS or feeder cells, which creates a bottleneck for therapeutic methods. We demonstrated that neurosphere-derived factor (NDF), which induces...

show abstract

Cystatin C and Cathepsin B Production by Alveolar Macrophages From Smokers and Nonsmokers

Cited by 31 publications

References 21 publications

Cathepsins in bleomycin-induced lung injury in rat

Cathepsins in bleomycin-induced lung injury in rat

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

A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells

Contact Info

Product

Resources

About