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Matrix metalloproteinases in destructive pulmonary pathology

Department of Infectious Diseases, Imperial College Hammersmith, London, UK

Correspondence to:
Correspondence to:
Dr P T G Elkington
Department of Infectious Diseases, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK; p.elkington{at}imperial.ac.uk

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have a number of important physiological roles including remodelling of the extracellular matrix, facilitating cell migration, cleaving cytokines, and activating defensins. However, excess MMP activity may lead to tissue destruction. The biology of MMP and the role of these proteases in normal pulmonary immunity are reviewed, and evidence that implicates excess MMP activity in causing matrix breakdown in chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), sarcoidosis, and tuberculosis is discussed. Evidence from both clinical studies and animal models showing that stromal and inflammatory cell MMP expression leads to immunopathology is examined, and the mechanisms by which excess MMP activity may be targeted to improve clinical outcomes are discussed.

Abbreviations: MMP, matrix metalloproteinase; ECM, extracellular matrix; COPD, chronic obstructive pulmonary disease; ARDS, acute respiratory distress syndrome; TB, tuberculosis; MTb, Mycobacterium tuberculosis; BAL, bronchoalveolar lavage

Keywords: matrix metalloproteinases; chronic obstructive pulmonary disease; tuberculosis; acute respiratory distress syndrome; sarcoidosis

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