Matrix metalloproteinases in destructive pulmonary pathology

Paul T G Elkington ^1* and Jon S Friedland ¹

¹ Imperial College, London, United Kingdom

^* To whom correspondence should be addressed. E-mail: p.elkington{at}imperial.ac.uk.

Accepted 1 October 2005

Abstract

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have multiple 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. Here we will review MMP biology and the role of these proteases in normal pulmonary immunity. We will then discuss evidence that implicates excess MMP activity in causing matrix breakdown in chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), sarcoidosis and tuberculosis. Evidence from both clinical studies and animal models demonstrating that stromal and inflammatory cell MMP expression leads to immunopathology will be examined. Finally we will discuss mechanisms by which excess MMP activity may be targeted to improve clinical outcomes.

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

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