Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies.
The persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions.
Rondeau
E
E
Service de Néphrologie et Association Claude Bernard, Hôpital Tenon, Paris, France.
Mougenot
B
B
Lacave
R
R
Peraldi
M N
MN
Kruithof
E K
EK
Sraer
J D
JD
D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D015849:Plasminogen Inactivators / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D015849:Plasminogen Inactivators; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator