Human sputum cathepsin B degrades proteoglycan, is inhibited by a2-macroglobulin and modulated by neutrophil elastase cleavage of cathepsin B precursor and cystatin C

Summary, in English

The high-Mr alkali-stable form of cathepsin B was purified from purulent human sputum. It was shown to solubilize proteoglycan monomer entrapped in polyacrylamide at a rate comparable with that of human lysosomal cathepsin B. Like the enzyme from lysosomes, sputum cathepsin B was bound by human alpha 2-macroglobulin, which inhibited its action on proteoglycan. Cystatin C in purulent sputum was shown to be the N-terminally truncated form generated by neutrophil elastase cleavage, and sputum cathepsin B was only weakly inhibited by recombinant cystatin C that had been cleaved by neutrophil elastase in vitro. Addition of neutrophil elastase to mucoid sputum led to a 5-fold increase in cathepsin B activity concomitant with a lowering in Mr of the cysteine proteinase from 40,000 to 37,000, i.e. the size of the active enzyme purified from purulent sputum. It is concluded that the high-Mr form of cathepsin B present in purulent sputum is a functional proteinase, unlike similar forms of the enzyme secreted by mammary gland in organ culture. The activity of cathepsin B in sputum is modulated by neutrophil elastase, by a combination of inhibitor inactivation and zymogen activation.

• Author: David J Buttle; Magnus Abrahamson; David Burnett; John S Mort; Alan J Barrett; Pamela M Dando; Susan L Hill
• Department/s: Division of Clinical Chemistry and Pharmacology
• Publishing year: 1991
• Language: English
• Pages: 325-331
• Publication/Series: Biochemical Journal
• Volume: 276
• Links: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1710889; http://www.biochemj.org/bj/276/bj2760325.htm
• Document type: Journal article
• Publisher: Portland Press
• Topic: Biochemistry and Molecular Biology
• Status: Published
• ISBN/ISSN/Other: ISSN: 0264-6021