Activation of the 92 kDa type IV collagenase by tissue kallikrein.
Type IV collagenases are secreted as latent 92 and 72 kDa proenzymes which are then activated extracellularly. The mechanisms by which they are activated in vivo are not clear. We have studied the activation of porcine endothelial cell type IV collagenases by tissue and plasma kallikrein, and found that tissue kallikrein was a very efficient activator of the 92 kDa type IV collagenase. Enzyme cleavage was observed at concentrations of tissue kallikrein as low as 0.1 microgram/ml. Plasma kallikrein had no effect. By comparison, plasmin, which has been proposed to be the physiological activator of interstitial collagenase and stromelysin, and elastase were much less effective, and high concentrations (plasmin at 100-200 micrograms/ml and elastase at 20 micrograms/ml) were required to cause only a limited cleavage which was not associated with an increase in activity, as observed by the gelatin-gel lysis assay. In addition tissue kallikrein was found by immunohistochemistry to be present in the extracellular matrix of the intima of porcine aortic vessel wall. These findings suggest that tissue kallikrein can be a potential activator of the 92 kDa type IV collagenase in vivo.
Desrivières
S
S
Unité 353 INSERM, Hopital Saint-Louis, Paris, France.
Lu
H
H
Peyri
N
N
Soria
C
C
Legrand
Y
Y
Ménashi
S
S
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation; D005341:Fibrinolysin / Q000494:pharmacology; D007150:Immunohistochemistry; D007610:Kallikreins / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013552:Swine; D020840:Tissue Kallikreins
D017077:Culture Media, Conditioned; D011480:Protease Inhibitors; D007610:Kallikreins; D020840:Tissue Kallikreins; D010196:Pancreatic Elastase; D005341:Fibrinolysin; D017364:Collagenases