Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function
Takanori Kuroiwa, Eizo Kakishita, Teruaki Hamano, Yasuro Kataoka, Yoshifumi Seto, Nobuo Iwata, Yasufumi Kaneda, Kunio Matsumoto, Toshikazu Nakamura, Takahiro Ueki, Jiro Fujimoto, Tsuyoshi Iwasaki
Takanori Kuroiwa, Eizo Kakishita, Teruaki Hamano, Yasuro Kataoka, Yoshifumi Seto, Nobuo Iwata, Yasufumi Kaneda, Kunio Matsumoto, Toshikazu Nakamura, Takahiro Ueki, Jiro Fujimoto, Tsuyoshi Iwasaki
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Article

Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function

Abstract

Acute graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation (BMT) and is characterized by hematopoietic dysfunction, immunosuppression, and tissue injury in the skin, liver, and intestinal mucosa. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, induces mitogenic and antiapoptotic activity in various epithelial cells and promotes hematopoiesis. Working in a murine model of acute GVHD, we performed repeated transfection of the human HGF cDNA into skeletal muscle and showed that this treatment inhibited apoptosis of intestinal epithelial cells and donor T-cell infiltration into the liver, thereby ameliorating the enteropathy and liver injury caused by acute GVHD. HGF also markedly suppressed IFN-γ and TNF-α expression in the intestine and liver and decreased the serum IL-12. Furthermore, extramedullary hematopoiesis by donor cells was increased, and the survival rate was improved. These results suggest that HGF may be useful for controlling acute GVHD after allogeneic BMT.

Authors

Takanori Kuroiwa, Eizo Kakishita, Teruaki Hamano, Yasuro Kataoka, Yoshifumi Seto, Nobuo Iwata, Yasufumi Kaneda, Kunio Matsumoto, Toshikazu Nakamura, Takahiro Ueki, Jiro Fujimoto, Tsuyoshi Iwasaki

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HGF caused a reduction of mortality (a) and weight loss (b) in a lethal ...
HGF caused a reduction of mortality (a) and weight loss (b) in a lethal GVHD model. Recipients were transplanted with 5 × 106 bone marrow cells plus 2 × 107 spleen cells from allogeneic (B6) donors after 9 Gy of TBI. Recipients transplanted with 5 × 106 bone marrow cells from syngeneic (BDF1) donors after TBI were used as BMT controls. HGF-HVJ liposomes (or PBS) were injected on day 0, 7, 14, and 21. PBS-treated syngeneic BMT (open squares; n = 4), HGF-treated syngeneic BMT (open circles; n = 4), PBS-treated GVHD (filled squares; n = 8), and HGF-treated GVHD (filled circles; n = 8) are indicated. P < 0.01 for survival after PBS injection versus HGF-HVJ liposomes injection and P < 0.05 for body weight from 4 weeks after BMT with PBS versus HGF-HVJ liposomes. Representative data from three similar experiments are shown.