The Effect Of Hepatocyte Growth Factor On Graft-versus-host Disease And Graft-versus-leukemia After Allogeneic Bone Marrow Transplantation In Acute Lymphoblastic Leukemic Mice

Objective The purpose of this experiment was to observe the effects of hepatocyte growth factor(HGF) on graft-versus-host disease(GVHD) and graft-versus-leukemia(GVL) after allogeneic bone marrow transplantation(allo-BMT) and related mechanism in allo-tansplanted acute lymphoblastic leukemic(ALL) mice.Methods To establish leukemia model by injecting L1210 acute lymphoblastic leukemia cell lineage originated from mouse into nude mice and BALB/c mice via their tail vein. transplantation of bone marrow of kunming mice to ALL model of nude mice and BALB/c mice was conditioned with 11Gy total body irradiation after the model established. 20 heath nude mice and 40 BALB/c mice were divided equally into either experimental group or control group. Group A and group B are control nude mice and experimental nude mice; and, group C and group D are control BALB/c mice and experimental BALB/c mice respectively; group C and D were divided equally into group C1,group C2 and group D1, D2. All experimental group mice (group B,group D) were injected subcutaneously with HGF(200ug/kg) once daily from day 0 to +7 after allo-BMT; and all control group mice (group A, group C) were injected subcutaneously with phosphate buffered saline (PBS) at same volum. the white blood cells were counted and their peripheral blood smear morphology from tail vein of all mice were observed everyday;The symptoms of GVHD of group C1 and groupD1 were investigated; The impact of HGF on CD₄⁺ and CD₈⁺ T cell after transplantation on day 8 was evaluated by flow cytometry; The level of tumor necrosis factor-α(TNF-α) which evidently related to GVHD and the levels of IFN- γ and IL-4,which closely related to Thl/Th2 cytokines of group C2 and D2, were evaluated by ELISA;the survial time of group C2 and D2 after transplantantion was recorded;the pathologic changes of liver, small intestine and skin associated with GVHD after allo-BMT in ALL mice were observed .Results HGF could decrease the quantity of CD₄⁺ T cell and increase the quantity of CD₈⁺T cell (P<0.01), the survival time of experimental mice increased obviously (P<0.05),the levels of TNF-a and IFN- Y decreased, and the levels of IL-4 increased in transplanted ALL mice (P<0.01);and the degree of GVHD after allo-BMT was reduced in experimental group mice. The rates of relapse of leukemia of group D2 were lower than that of group C2.Conclusion HGF could alleviate GVHD and retain GVL effect after allo-BMT, that was correlated with HGF which can adjust Thl/Th2-related cytokines balance after allo-BMT.