The Role of the Kininogens as Cysteine Proteinase Inhibitors in Local and Systemic Inflammation

Assfalg-Machleidt, Irmgard; Billing, A.; Fröhlich, D.; Nast-Kolb, D.; Joka, Th.; Jochum, Marianne; Machleidt, Werner

doi:10.1007/978-3-0348-7321-5_40

Cited by 14 publications

(16 citation statements)

References 8 publications

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“…It has been reported that the control of CB in blood depends critically on the concentration of active CC and to a lesser extent on the concentration of kininogens (Assfalg-Machleidt et al, 1992). This is consistent with the assessment of the levels of CB/kininogen complexes by specific ELISA in blood of patients manifesting an acute phase response (Takeda et al, 1992).…”

Section: Discussionsupporting

confidence: 85%

Cathepsin B/Cystatin C Complex Levels in Sera from Patients with Lung and Colorectal Cancer

Zore¹,

Krašovec²,

Cimerman³

et al. 2001

Biological Chemistry

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A sandwich-type ELISA has been developed for quantification of the complex between the cysteine proteinase cathepsin Β (CB) and its reversible tight-binding inhibitor cystatin C (CC) in normal and pathological sera. The assay is based on a combination of catching Ab (3E1), raised against CB, and a horseradish peroxidase-labelled detection Ab (1A2), raised against CC. Only the CB/CC complex is able to evoke a signal in this assay. The detection limit of the assay was 15.5 ΠΜ and the working range between 31.3-200 nM. The within and between-run coefficients of variance (CV) varied from 4.7% to 9.4% and 11% to 12.8%, respectively, demonstrating satisfactory reproducibility of the method. The concentration of the CB/CC complex was determined in sera from 90 healthy controls, 32 patients with non-cancerous lung diseases, 148 patients with lung and 32 patients with colorectal cancer. The CB/CC complex was significantly less abundant in sera of patients bearing malignant lung tumours than in those with non-cancerous lung diseases or healthy controls (p<0.001). In colorectal cancer sera its level was significantly lower in advanced stages C and D than in early Dukes' stages A and Β (p=0.02). Our results show that the increased levels of CB in malignant sera are not impaired effectively by CC and support the hypothesis of hindered inhibitory capability during cancer progression.Keywords: Cathepsin B/Colorectal Cancer/Complex/ Cystatin C/Lung Cancer. Yan, S., Sameni, M. and Sloane, B.F. (1998). Cathepsin Β in human tumor progresión: a review. Biol. Chem. 379, 113-123. Warwas, M., Haczynska, H., Gerber, J. and Nowak, M. (1997). Cathepsin B-like activity as a serum tumor marker in ovarian carcinoma. Eur. J. Clin. Chem. Clin. Biochem. 35, 301 -304.

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Section: Discussionsupporting

confidence: 85%

Cathepsin B/Cystatin C Complex Levels in Sera from Patients with Lung and Colorectal Cancer

Zore¹,

Krašovec²,

Cimerman³

et al. 2001

Biological Chemistry

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“…The residual CP inhibitory capacity was evaluated by measuring the ability of BALFs to inhibit exogenous papain (titrated with E‐64 [ trans ‐epoxysuccinyl‐L‐leucylamido‐(4‐guanidino)butane]; see the Materials and methods section), as described by Assfalg‐Machleidt et al (1992). The average CPI (CP inhibitor) value (expressed as inhibitory site equivalents) was 147±23 nM (median 146 nM).…”

Section: Resultsmentioning

confidence: 99%

Active cathepsins B, H, K, L and S in human inflammatory bronchoalveolar lavage fluids

Serveau-Avesque

Martino

Hervé-Grépinet

et al. 2006

Biology of the Cell

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Background information. Chronic inflammation and tissue remodelling result from an imbalance between proteolytic enzymes and their inhibitors in the lungs in favour of proteolysis. While many studies have examined serine proteases (e.g. cathepsin G and neutrophil elastase) and matrix metalloproteases, little is known about the role of papain-like CPs (cysteine proteases). The present study focuses on the thiol-dependent cathepsins (CPs) and their specific cystatin-like inhibitors [CPIs (CP inhibitors)] in human inflammatory BALFs (BAL fluids, where BAL stands for broncho-alveolar lavage).Results. Cathepsins B, K and S found were mostly zymogens, whereas cathepsins H and L were predominantly in their mature forms. Little immunoreactive cystatin C was found and the high-and low-molecular-mass ('weight') kininogens were extensively degraded. The BALF procathepsins B and L could be activated autocatalytically, indicating that alveolar fluid pro-CPs are reservoirs of mature enzymes. Hydrolysis patterns of 7-amino-4-methylcoumarin-derived peptide substrates showed that extracellular alveolar CPs remain proteolytically active, and that cathepsins B and L are the most abundant thiol-dependent endoproteases. The CP/CPI balance was significantly tipped in favour of cathepsins (3-or 5-fold), as confirmed by the extensive CP-dependent degradation of exogenous kininogens by BALFs. Conclusions.Although their importance for inflammation remains to be clarified, the presence of active cathepsins L, K and S suggests that they contribute to the extracellular breakdown of the extracellular matrix.

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“…Some endogenous inhibitors of cathepsin B can be dissociated from the protease by simple dilution (65,75). Incubation of rat liver homogenates with increasing volumes of buffer results in a gain of cathepsin B activity until an asymptote is reached (65).…”

Section: Discussionmentioning

confidence: 99%

Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus Infection

Ebert

Kopecky-Bromberg

Dermody

2004

Journal of Biological Chemistry

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The Role of the Kininogens as Cysteine Proteinase Inhibitors in Local and Systemic Inflammation

Cited by 14 publications

References 8 publications

Cathepsin B/Cystatin C Complex Levels in Sera from Patients with Lung and Colorectal Cancer

Cathepsin B/Cystatin C Complex Levels in Sera from Patients with Lung and Colorectal Cancer

Active cathepsins B, H, K, L and S in human inflammatory bronchoalveolar lavage fluids

Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus Infection

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