Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer

Rayment, E. A. and Upton, Z. and Shooter, G. K. (2008) Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer. British Journal of Dermatology, 158 (5). pp. 951-961. ISSN 0007-0963


Background: The pathology of chronic wounds is often characterized by elevated levels of proinflammatory cytokines [e.g. tumour necrosis factor (TNF)-α and interleukin (IL)-1β], proteases [e.g. matrix metalloproteinases (MMPs)] and neutrophil elastase. MMPs specifically have been implicated by a number of studies as the major protease family responsible for the degradation of key factors critical to the ulcer's ability to heal. Objectives: To assess individual MMPs in chronic wound fluid (CWF) in order to develop improved treatments for chronic ulcers.
Methods: Collagen type I and IV zymography, immunoprecipitation followed by a substrate activity assay, and an indirect enzyme-linked immunosorbent assay were all used to analyse MMP levels in CWF.
Results: Our studies demonstrate that there is excessive protease activity in CWF compared with both human serum and acute wound fluid (AWF), which can be specifically attributed to MMPs as determined through a MMP-inhibitor study. Multiple MMPs were immunoprecipitated from the CWF samples and MMP-9 was identified as the predominant protease in CWF, with significantly elevated activity levels in CWF compared with AWF. In addition, the clinical status of the ulcer is directly associated with the amounts of MMP-9 present in the wound fluid. Therefore, this study suggests that higher levels of MMP-9 in chronic wound fluid correlate with a clinically worse wound. Conclusions: In view of these results, it is hypothesized that a specific inhibitor of MMP-9 could potentially be more therapeutically effective than general MMP inhibitors in modulating chronic ulcers towards a healing state.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2008 The Authors. Permanent restricted access to published version due to publisher copyright policy.
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 06 Nov 2014 00:17
Last Modified: 04 Mar 2015 05:47
Uncontrolled Keywords: chronic leg ulcer; gelatinase-B; matrix metalloproteinase; wound healing
Fields of Research (2008): 11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified
11 Medical and Health Sciences > 1103 Clinical Sciences > 110316 Pathology (excl. Oral Pathology)
11 Medical and Health Sciences > 1108 Medical Microbiology > 110801 Medical Bacteriology
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320220 Pathology (excl. oral pathology)
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology
Socio-Economic Objectives (2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases
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