Expression and localization of plasminogen activator inhibitor 1 mRNA in transplant kidneys

Fibrinolysis in renal transplant rejection has not been systematically investigated but is known to be impaired. By an in situ hybridization technique, we have studied gene expression of plasminogen activator inhibitor 1 (PAI-1) in human renal tissue showing severe acute vascular rejection (n = 8), clinically irreversible (chronic) vascular rejection (n = 3), mild vascular rejection (n = 8), parenchymal rejection (n = 4), 'normal' kidneys (n = 6), and non-rejecting kidneys (n = 6). The results showed that in 7/8 cases showing severe acute vascular rejection and in all three chronic vascular rejection cases, PAI-1 mRNA was expressed by endothelial cells of arterioles and arteries, and interstitial inflammatory cells but was not detectable in any other groups. The expression of PAI-1 was frequently associated with areas of haemorrhage. Expression of PAI-1 might be expected to promote thrombosis and ischaemia, the catastrophic consequence of severe vascular rejection. In irreversible chronic rejection, this seems to be the principal mode of action. However, our observation that there is expression of PAI-1 in areas of haemorrhage in severe acute vascular rejection may suggest an additional potentially protective role, if it were produced as a response to haemorrhage.