MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers.

Abstract

BACKGROUND:

The initial cleavage of collagen by collagenase represents the rate-limiting step in the degradation of this central extracellular matrix protein. Chronic nonhealing ulcers, especially pressure ulcers, typically contain elevated levels of collagenolytic activity. However, there have been no detailed attempts to identify the source of these collagenases and their activity either in normal healing wounds or in chronic nonhealing ulcers.

MATERIALS AND METHODS:

Levels of the matrix metalloproteinases, MMP-1 and MMP-8, and the tissue inhibitor of matrix metalloproteinases, TIMP-1, were measured in fluids and tissues of healing human wounds and nonhealing ulcers by ELISA. Relative MMP-1 and MMP-8 levels were also analyzed by substrate preference in a functional assay.

RESULTS:

The patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct, with MMP-8 appearing in significantly greater amounts than MMP-1. Chronic nonhealing ulcers were characterized by significantly higher levels of MMP-1 and MMP-8, and lower levels of TIMP-1, than in healing wounds. Levels of both MMP-1 and MMP-8 varied greatly in chronic ulcers, although MMP-8 was always the predominant collagenase present in these wounds. Interestingly, these collagenases were present almost exclusively in their inactive forms in healing wounds, whereas nonhealing ulcers possessed significant levels of the active forms of these enzymes.

CONCLUSIONS:

These results clearly demonstrate that the neutrophil-derived MMP-8 is the predominant collagenase present in normal healing wounds and suggest that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic ulcers. In addition, excessive collagenolytic activity in chronic ulcers is made possible, partly because of the reduced levels of the inhibitor, TIMP-1.

• Authors: B C Nwomeh, H X Liang, I K Cohen, D R Yager
• Journal: The Journal of surgical research (J Surg Res) Vol. 81 Issue 2 Pg. 189-95 (Feb 1999) ISSN: 0022-4804 [Print] United States
• PMID: 9927539 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1999 Academic Press.

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Collagenases
• Matrix Metalloproteinase 8
• Matrix Metalloproteinase 1

Topics

• Adult
• Chronic Disease
• Collagenases (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Mastectomy
• Matrix Metalloproteinase 1
• Matrix Metalloproteinase 8
• Middle Aged
• Pressure Ulcer (enzymology, physiopathology)
• Skin (enzymology, injuries)
• Surgical Flaps
• Time Factors
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Varicose Ulcer (enzymology, physiopathology)
• Wound Healing (physiology)
• Wounds and Injuries (enzymology, physiopathology)