cqvip:Background:The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing . It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinol ysis. Objectives:The present study was conducted to characterizethe spatial dis tribution of the various plasminogen activation system components in chronic ulc ers and acute, well-granulating wounds. Methods:The expression of uPA, tPA, ur okinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitron ectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic v enous ulcers, five decubitus ulcers, five well-granulating acute wounds and fiv e normal skin samples. Results:In chronic venous leg ulcers tPA mRNA was detect ed in basal and suprabasal keratinocytes at the leading wound edge, while in wel l-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a f ew keratinocytes. However, tPA was widely expressed in fibroblast-and macrophag e-like cells in the stroma of well-granulating wounds, while less tPA was dete cted in the granulation tissue of chronic ulcers. tPA mRNA and protein were loca lized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocyte s in chronic ulcers vs. nor-mally granulating wounds were found, their expressi ons were more pronounced in the granulation tissue of well-granulating wounds. Conclusions:These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of th e wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the g ranulation tissue.
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