Plasminogen activation in healing human wounds.
Tissue injury is followed by formation of a provisional, fibrin-containing matrix. It is later on replaced by granulation tissue. Replacement involves extracellular proteolysis by fibrinolytic enzymes. Plasmin is a fibrinolytic proteinase and is generated from ubiquitous plasminogen by cell-derived urokinase-type (uPA) or tissue-type (tPA) plasminogen activator. To explore the cells and components involved in plasminogen activation, we have performed a combined immunohistological and zymographic study on human skin wounds produced iatrogenically by debridement. The fibrin(ogen)-specific staining indicated the progressive removal of a fibrin-containing provisional matrix. Plasmin(ogen) was present over the entire observation period. It was diffusely distributed and also displayed a conspicuous association with cells of the granulation tissue, in particular with monocytes/macrophages and fibroblasts. Also, uPA was associated with monocytes/macrophages and fibroblasts, whereas the uPA-receptor (uPA-R) was stained in monocytes/macrophages only. The uPA was potentially active as indicated by zymography. No tPA-specific staining was found. The findings point at the importance of monocytes/macrophages and fibroblasts in uPA-mediated plasminogen activation in healing human skin wounds.
Schäfer
B M
BM
Institut für Immunologie und Serologie, Universität Heidelberg, Germany.
Maier
K
K
Eickhoff
U
U
Todd
R F
RF
Kramer
M D
MD
D000328:Adult; D001706:Biopsy; D005337:Fibrin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D005341:Fibrinolysin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010960:Plasminogen Activators / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005337:Fibrin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator