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Published online before print September 7, 2006
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,1
* AIDS Pathogenesis Research Program, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia;
Department of Immunology, Monash University, Melbourne, Victoria, Australia; and
Department of Medicine, Monash University, Melbourne, Victoria, Australia
1 Correspondence: AIDS Pathogenesis and Clinical Research Program, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Rd., Melbourne 3004, Australia. E-mail: crowe{at}burnet.edu.au
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are a subfamily of metzincins. Matrix metalloproteinases are responsible for much of the turnover of extra-cellular matrix components and are key to a wide range of processes including tissue remodeling and release of biological factors. Imbalance between the MMPs and endogenous tissue inhibitors of metalloproteinases (TIMPs) can result in dysregulation of many biologic processes and lead to the development of malignancy, cardiovascular disease, and autoimmune and inflammatory disorders. MMP production by monocyte/macrophages is dependent on the cell type, state of differentiation, and/or level of activation and whether they are infected, e.g., by HIV-1. MMP expression by HIV-1 infected monocytes and macrophages may alter cellular trafficking and contribute to HIV-associated pathology such as HIV-associated dementia (HAD). This review will provide a classification of the MMP super-family with particular reference to those produced by monocyte/macrophages, describe their regulation and function within the immune system, and indicate their possible roles in the pathogenesis of disease, including HIV-associated dementia.
Key Words: pathogenesis • cell migration • HIV-associated dementia • chemokines • cytokines
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