STIMULATION BY HISTAMINE OF TPA-DEPENDENT HEPATOCYTE GROWTH-FACTOR PRODUCTION IN PROMYELOCYTIC LEUKEMIA HL-60 CELLS

Hepatocyte growth factor (HGF) is most likely a physiological hepatotr ophic factor that triggers regeneration of the injured liver. Histamin e may also be important in the pathophysiology of the injured liver. P reviously we showed that histamine production was increased in liver m acrophages of mice injected with CCl4, a well-known hepatotoxin. There fore, it is likely that the biological actions of histamine in repairi ng processes of the injured liver are mediated by HGF. This study was aimed at examining the effects of histamine on production of HGF using , as a model, the human promyelocytic leukemia cells, HL-60. 12-o-Tetr adecanoylphorbol-13-acetate (TPA) markedly stimulated HGF production a nd release from the cells; the maximal amount of HGF was released at a concentration of 3 ng/ml of TPA. Histamine significantly stimulated t he TPA-induced HGF production and release in these cells, depending on incubation time and its dose. These actions of histamine were abrogat ed by a H2 receptor antagonist, ranitidine.