Matrix metalloproteinases, gelatinase and collagenase, in chronic leg ulcers.
Although extracellular proteolysis is a prerequisite for normal wound healing, uncontrolled proteolytic tissue destruction appears to be a pathogenic factor in non-healing wounds. The aim of our study was to compare the activities of the serine proteinases of polymorphonuclear origin, elastase and cathepsin G, and the metalloproteinases, gelatinase and collagenase, in chronic leg ulcer exudate (10 patients) and acute wound fluid (6 patients). Serine proteinase activities were low in leg ulcer exudates but very high in some but not all acute wound fluids. Total collagenase activity, measured as activity against type I collagen monitored by SDS-PAGE and densitometry, was higher in chronic leg ulcer exudate than in acute wound fluid and its degree of autoactivation was relatively high. Doxycycline inhibition studies suggested that the collagenase activity in chronic leg ulcer exudate was MMP-1 ("fibroblast-type") and not MMP-8 ("neutrophil-type"). Zymographic analysis of the gelatinolytic enzymes in acute wound fluid showed a progressive increase from the day of operation to postoperative day 5, but the degree of activity was lower than in chronic leg ulcer exudate and the low molecular mass activation products were faint. The leg ulcer gelatinase profiles were characterized by high expression of 92/82- and 72/62-kDa duplex bands and by the presence of low molecular mass activation products. Leg ulcer collagenase seems to be derived from mononuclear rather than polymorphonuclear cells, which are known to be involved in acute wound healing. In conclusion, the present study shows that gelatinase and collagenase, but not elastase and cathepsin G are found in chronic leg ulcer exudate.
Weckroth
M
M
Department of Virology, Haartman Institute, University of Helsinki, Finland.
Vaheri
A
A
Lauharanta
J
J
Sorsa
T
T
Konttinen
Y T
YT
D000368:Aged; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D002908:Chronic Disease; D017364:Collagenases / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007871:Leg Ulcer / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000378:metabolism; D012697:Serine Endopeptidases
D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D017364:Collagenases; D018093:Gelatinases; D004318:Doxycycline