IMMUNOLOCALIZATION OF HEPARIN-BINDING GROWTH-FACTORS (HBGF) TYPES-1 AND 2 IN RAT-LIVER - SELECTIVE HYPEREXPRESSION OF HBGF-2 IN CARBON TETRACHLORIDE-INDUCED FIBROSIS

Ito cells play a major role in liver fibrosis but the mechanisms contr olling their activation in vivo are poorly understood. Heparin-binding growth factors (HBGF) types 1 and 2 are mitogenic for cultured Ito ce lls. They have been found in liver extracts but their cellular localiz ation is unknown. We have studied by immunohistochemistry HBGF-1 and - 2 expression in normal rat liver and in carbon tetrachloride (CCl4)-in duced fibrosis. In normal liver, HBGF-1 was present only in sinusoidal cells whereas HBGF-2 was also detected in endothelial cells lining ma jor vessels. At the acute stage of CCl4 intoxication, HBGF-2 was expre ssed in centrilobular clusters of mononuclear phagocytes that were sur rounded by many HBGF-2-negative Ito cells. In the later stages, HBGF-2 was expressed by Ito cells within the fibrous bands. No modulation of HBGF-1 expression was noted at any stage. These results suggest that (1) at the acute stage of CCl4 intoxication, HBGF-2 produced by mononu clear phagocytes could participate in the recruitment of Ito cells; an d (2) during the CCl4-induced fibrotic process, HBGF-2 could contribut e to Ito cell proliferation and the synthesis of fibrosis components. In this in vivo model of hepatic fibrosis, the hyperexpression of HBGF -2 is a relatively specific event since the expression of a structural ly related molecule, HBGF-1 was not modulated.