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The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease

James Hogg Research Laboratories, Providence Heart + Lung Institute at St. Paul's Hospital and Department of Medicine, University of British Columbia, Vancouver, BC, Canada

Shawna V. Vickerman

James Hogg Research Laboratories, Providence Heart + Lung Institute at St. Paul's Hospital and Department of Medicine, University of British Columbia, Vancouver, BC, Canada

David J. Granville

James Hogg Research Laboratories, Providence Heart + Lung Institute at St. Paul's Hospital and Department of Medicine, University of British Columbia, Vancouver, BC, Canada

S. F. Paul Man

James Hogg Research Laboratories, Providence Heart + Lung Institute at St. Paul's Hospital and Department of Medicine, University of British Columbia, Vancouver, BC, Canada

Don D. Sin

James Hogg Research Laboratories, Providence Heart + Lung Institute at St. Paul's Hospital and Department of Medicine, University of British Columbia, Vancouver, BC, Canada, dsin{at}mrl.ubc.ca

Chronic obstructive pulmonary disease (COPD) is a highly prevalent inflammatory lung condition characterized by airways disease and emphysema, and the precise mechanism of pathogenesis is poorly understood. The consistent features of COPD include protease-antiprotease imbalance, inflammation and accelerated aging caused by apoptosis or senescence. One family of molecules involved in all of these processes is the granzymes, serine proteases with the best-known member being granzyme B (GzmB). The majority of GzmB is released unidirectionally towards target cells, but GzmB can also be released nonspecifically and escape into the extracellular environment. GzmB is capable of cleaving extracellular matrix (ECM) proteins in vitro, and the accumulation of GzmB in the extracellular milieu during chronic inflammation in COPD could contribute to ECM degradation and remodelling and, consequently, the emphysematous phenotype in the lung. Preliminary studies suggest that increased GzmB expression is associated with increased COPD severity, and this may represent a promising new target for drug and biomarker discovery in COPD. In this paper, we review the potential pathogenic contributions of GzmB to the pathogenesis of COPD.

Key Words: granzyme B • COPD • pathogenesis • proteases • inflammation • senescence • apoptosis

This version was published on June 1, 2009

Therapeutic Advances in Respiratory Disease, Vol. 3, No. 3, 113-129 (2009)
DOI: 10.1177/1753465809341965


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