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Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages.

Punturieri A, Filippov S, Allen E, Caras I, Murray R, Reddy V, Weiss SJ - J. Exp. Med. (2000)

Bottom Line: Simultaneously, MDMs increased the expression of vacuolar-type H(+)-ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form.MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity.Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

ABSTRACT
Human macrophages mediate the dissolution of elastic lamina by mobilizing tissue-destructive cysteine proteinases. While macrophage-mediated elastin degradation has been linked to the expression of cathepsins L and S, these cells also express cathepsin K, a new member of the cysteine proteinase family whose elastinolytic potential exceeds that of all known elastases. To determine the relative role of cathepsin K in elastinolysis, monocytes were differentiated under conditions in which they recapitulated a gene expression profile similar to that observed at sites of tissue damage in vivo. After a 12-d culture period, monocyte-derived macrophages (MDMs) expressed cathepsin K in tandem with cathepsins L and S. Though cysteine proteinases are acidophilic and normally confined to the lysosomal network, MDMs secreted cathepsin K extracellularly in concert with cathepsins L and S. Simultaneously, MDMs increased the expression of vacuolar-type H(+)-ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form. MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity. Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.

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Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages.

Punturieri A, Filippov S, Allen E, Caras I, Murray R, Reddy V, Weiss SJ - J. Exp. Med. (2000)

© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193285&req=5

Bottom Line: Simultaneously, MDMs increased the expression of vacuolar-type H(+)-ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form.MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity.Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

ABSTRACT
Human macrophages mediate the dissolution of elastic lamina by mobilizing tissue-destructive cysteine proteinases. While macrophage-mediated elastin degradation has been linked to the expression of cathepsins L and S, these cells also express cathepsin K, a new member of the cysteine proteinase family whose elastinolytic potential exceeds that of all known elastases. To determine the relative role of cathepsin K in elastinolysis, monocytes were differentiated under conditions in which they recapitulated a gene expression profile similar to that observed at sites of tissue damage in vivo. After a 12-d culture period, monocyte-derived macrophages (MDMs) expressed cathepsin K in tandem with cathepsins L and S. Though cysteine proteinases are acidophilic and normally confined to the lysosomal network, MDMs secreted cathepsin K extracellularly in concert with cathepsins L and S. Simultaneously, MDMs increased the expression of vacuolar-type H(+)-ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form. MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity. Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.

Show MeSH
Related in: MedlinePlus