INTRAHEPATIC DISTRIBUTION OF TRANSFORMING GROWTH FACTOR-ALPHA (TGF-ALPHA) DURING LIVER-REGENERATION FOLLOWING CARBON TETRACHLORIDE- INDUCED NECROSIS

The distribution of transforming growth factor-alpha (TGFalpha) in rat liver during regeneration was studied immunohistochemically using two antibodies, one a polyclonal (26T) raised against a synthetic peptide corresponding to the 17 C-terminal amino acids of the mature rat protein, and the other a monoclonal (Ab-2) raised against recombinant human protein. In normal liver, immunoreactive TGFalpha was detected in perivenular hepatocytes using both antibodies. No sinusoidal cells were found to contain the peptide. In response to carbon tetrachloride (CCl4)-induced necrosis, an initial increase in the intensity of immunoreactivity was noted at 24 h following exposure to the toxin. This coincided with the period immediately preceding the peak of hepatocyte proliferation; Ab-2 immunoreactive cells outnumbered 26T-positive cells. Thereafter there was a reduction in the number of TGFalpha-positive cells, but by day 4 the level of immunoreactivity had returned to that of normal liver. Using bromodeoxyuridine labelling, spatial and temporal relationships between TGFalpha expression and cell proliferation were identified, supporting the concept that this peptide plays an important role in the in vivo regenerative response to hepatic injury via an autocrine mechanism.