Human hepatocyte growth factor in plasma from patients with fulminant hepatic failure

Plasma from patients with fulminant hepatic failure obtained during plasma exchange therapy, like their serum, demonstrated marked stimulatory activity on DNA synthesis in cultured rat hepatocytes. Heat treatment at 56 degrees C for 30 min did not affect this activity of the plasma, but reduced that of the serum. This growth-promoting activity was confirmed by showing that the patients' serum and plasma increased the labeling index with [3H]thymidine and the total number of nuclei in hepatocyte cultures. The activity of pooled active fractions obtained by gel filtration of the heated plasma was lost completely on heat treatment at 80 degrees C for 10 min or on treatment with trypsin or chymotrypsin, which suggests that it was due to a protein. The human hepatocyte growth factor was purified about 600-fold from heated plasma of a patient by ammonium sulfate precipitation and chromatographies on Affi-Gel Blue and hydroxylapatite. The maximum effect of this partially purified factor on DNA synthesis in cultured hepatocytes was greater than that of epidermal growth factor. The molecular weight of the hepatocyte growth factor was about 85,000 as determined by SDS-PAGE.