Cathepsin D Activity Is Increased in Alveolar Macrophages and Bronchoalveolar Lavage Fluid of Smokers

Chang, Jui Cheng; Yoo, Ok Hi; Lesser, Marvin

doi:10.1164/ajrccm/140.4.958

Cited by 37 publications

(26 citation statements)

References 7 publications

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“…This is the first evidence indicating association of Cath H expression or regulation with cigarette smoking in human lung cancer and is consistent with previous studies revealing an increase of Cath B and L activity in lung tissue of smokers (Knoch et al, 1994;Werle et al, 1995), in their alveolar macrophages and alveolar lavage fluid (Chang et al, 1986;Takahashi et al, 1993) as well as in alveolar macrophages and bronchoalveolar lavage fluid of rats exposed to cigarette smoke Lesser et al, 1989;Chapman et al, 1997). Furthermore, Yukio Ishii (1991aIshii ( , 1991b clearly demonstrated that Cath H is secreted mainly with surfactant from Type II alveolar epithelial cells and alveolar macrophages of rat lung.…”

Section: Discussionsupporting

confidence: 92%

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

et al. 2000

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Summary In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg -1 protein, P < 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P < 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours.

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Section: Discussionsupporting

confidence: 92%

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

et al. 2000

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“…Lysosomal proteinases intracellularly complete the extracellular cleavage of collagens, elastin and proteoglycan core proteins by serine and metalloproteinases [7]. They are partially secreted into the extracellular space and the bronchoalveolar lavage fluid (BALF) [6,7,14,15]. The activities of cysteine proteinases are controlled by their endogenous inhibitors, the cystatins [6,7,16].…”

mentioning

confidence: 99%

Cathepsins in bleomycin-induced lung injury in rat

Koslowski¹,

Knoch²,

Kuhlisch³

et al. 2003

Eur Respir J

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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.

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“…This aspartyl endoprotease is closely associated with tumour progression in some human malignancies including Lung cytotoxicity of combined exposure to refractory ceramic fibres and cigarette smoke 384 lung adenocarcinoma 29 , it is overexpressed in inflammatory status 30 and modulated by inflammatory mediators. Cigarette smoke was described as a potent inducer of this enzyme activity in AM 31 . Examination of the effect of RCF cigarette smoke on cells in lung tissue results into the following conclusions: (i) The expected cytotoxicity of RCF was confirmed by the significant decrease in viability of AM, significant increase in CATD activity in cfBALF, and significant increase in ACP and CATD activity in BALF cells; (ii) Cytotoxic activity of cigarette smoke was demonstrated by the significant decrease in viability of AM, significant decrease in phagocytic activity of AM, significant increase of ACP and CATD activity in cfBALF, and significant increase of ACP and CATD activity in BALF cells.…”

Section: Figmentioning

confidence: 99%

Lung Cytotoxicity of Combined Exposure to Refractory Ceramic Fibres and Cigarette Smoke

Černá¹,

Hurbánková²,

Kovačíková³

et al. 2005

BIOMED PAP

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Changes in some lung cytotoxic parameters after exposure to refractory ceramic fibres (RCF) or to cigarette smoke (S) and after combined exposure to RCF+S were studied in male Wistar rats in order to evaluate their potential adverse health effects. Four groups of rats were treated as follows : 1) intratracheally instilled by saline solution (0.4 ml); 2) intratracheally instilled by 4 mg of RCF; 3) exposed only to S (85 mg of total particulate matter/m 3 air ) for two hours daily; 4) exposed to RCF+S. After 6 months the animals were exsanguinated and the bronchoalveolar lavage (BAL) was perfomed. Viability and phagocytic activity of alveolar macrophages (AM), activity of lactate dehydrogenase (LDH) in cell-free BAL fluid (cf -BALF), acid phosphatase (ACP) and cathepsin D (CATD) in cfBALF, in BALF cells and in the lung tissue were estimated. Viability of AM was depressed by every type of exposure with RCF+S effect being at least additive. Phagocytic activity of AM increased in the presence of RCF. No significant changes in LDH activity were found. Activities of lysosomal enzymes measured in the lung tissue homogenates were not significantly changed, but those in the cfBALF increased especially after exposure to S with most expressive increase in BALF cells after exposure to S and RCF+S. In the case of CATD the effect of RCF+S was more than additive. The results point out to the persistence of the RCF exposure cytotoxic effects and their amplification by cigarette smoke.

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Cathepsin D Activity Is Increased in Alveolar Macrophages and Bronchoalveolar Lavage Fluid of Smokers

Cited by 37 publications

References 7 publications

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

Cathepsins in bleomycin-induced lung injury in rat

Lung Cytotoxicity of Combined Exposure to Refractory Ceramic Fibres and Cigarette Smoke

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