DISTRIBUTION OF PLASMINOGEN-ACTIVATOR INHIBITOR IN NORMAL LIVER, CIRRHOTIC LIVER, AND LIVER WITH METASTASES

Aims-To examine the distribution of PAI-1 antigen in normal and cirrho tic liver and liver with metastases. Methods-Sections of normal and ci rrhotic liver and Liver with metastases were stained using the alkalin e phosphatase antialkaline phosphatase (APAAP) technique and monoclona l antibody specific for plasminogen activator inhibitor (PAI-1). Resul ts-PAI-1 antigen was identified as discrete granules in the cytoplasm of hepatocytes in normal liver, particularly around portal tracts and central veins of the liver lobule. In cirrhotic liver a striking reduc tion of PAI-1 antigen was noted. In liver with metastases increased am ounts of PAI-1 antigen were concentrated in hepatocytes around the mar gins of malignant deposits. Conclusions-Cirrhotic liver contains consi derably less PAI-1 antigen than does normal liver, despite raised plas ma concentrations of PAI-1. This may reflect release of hepatic PAI-1 into the circulation or decreased clearance of PAI-1 from the plasma. Secondary malignant deposits in the liver seem to stimulate production of PAI-1 in adjacent hepatocytes. This may influence the invasive pro cess and may contribute to the thrombotic tendency associated with mal ignancy.