The paradox of matrix metalloproteinases in infectious disease
The paradox of matrix metalloproteinases in infectious disease
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that perform multiple roles in the normal immune response to infection. MMPs facilitate leucocyte recruitment, cytokine and chemokine processing, defensin activation and matrix remodelling. However, excess MMP activity following infection may lead to immunopathology that causes host morbidity or mortality and favours pathogen dissemination or persistence. Here, we review the normal functions of MMPs in immunity and then discuss viral and bacterial infections where excess MMP activity has been implicated in pathology, specifically examining HIV, HTLV-1, hepatitis B, endotoxin shock, Helicobacter pylori and Mycobacterium tuberculosis. Tissue destruction may be exacerbated further by bacterial-derived enzymes which activate the host pro-MMPs. Finally, the potential for therapeutic targeting of excess MMP activity in infection is considered.
HIV, immunopathology, infection, matrix metalloproteinase, tuberculosis
12-20
Elkington, P. T. G.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
O'Kane, C. M.
fafe626f-9df9-47c4-ba2f-cb9f23abaa07
Friedland, J. S.
9dd800b0-70cb-4793-988f-a24e387b4e46
October 2005
Elkington, P. T. G.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
O'Kane, C. M.
fafe626f-9df9-47c4-ba2f-cb9f23abaa07
Friedland, J. S.
9dd800b0-70cb-4793-988f-a24e387b4e46
Abstract
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that perform multiple roles in the normal immune response to infection. MMPs facilitate leucocyte recruitment, cytokine and chemokine processing, defensin activation and matrix remodelling. However, excess MMP activity following infection may lead to immunopathology that causes host morbidity or mortality and favours pathogen dissemination or persistence. Here, we review the normal functions of MMPs in immunity and then discuss viral and bacterial infections where excess MMP activity has been implicated in pathology, specifically examining HIV, HTLV-1, hepatitis B, endotoxin shock, Helicobacter pylori and Mycobacterium tuberculosis. Tissue destruction may be exacerbated further by bacterial-derived enzymes which activate the host pro-MMPs. Finally, the potential for therapeutic targeting of excess MMP activity in infection is considered.
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Published date: October 2005
Keywords:
HIV, immunopathology, infection, matrix metalloproteinase, tuberculosis
Organisations:
Faculty of Medicine
Identifiers
Local EPrints ID: 340670
URI: http://eprints.soton.ac.uk/id/eprint/340670
ISSN: 0009-9104
PURE UUID: ba1c1936-76a0-4a5f-a150-d86ae26f733c
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Date deposited: 29 Jun 2012 09:27
Last modified: 15 Mar 2024 03:43
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Author:
C. M. O'Kane
Author:
J. S. Friedland
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