Effect of macrophage migration inhibitory factor (MIF) on acute graft-versus-host disease in a murine model of allogeneic stem cell transplantation.
Macrophage migration inhibitory factor (MIF) may play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We examined whether MIF has an influence on the development of aGVHD and survival using BALB/c-based MIF knock-out (MIF KO) mice. Although MIF expression was observed in lymphocytes that had infiltrated the liver during aGVHD in both wild-type (WT) and MIF KO mice that received bone marrow cells (BM) and spleen cells (SP) from C57BL/6N mice, no significant difference was found in severity of aGVHD or survival rate between the two groups of mice. However, MIF level had decreased at 1 week after HSCT when MIF KO mice were used as the recipients. In the experiment using MIF KO mice as the donors, the recipient mice transplanted with BM and SP from MIF KO mice had significantly lower aGVHD scores on days 14, 21, and 35 than those in the recipient mice transplanted with BM and SP from WT-BALB/c mice. Histopathological findings supported these observations, showing that the bile ducts and lobules in the liver were destroyed by infiltrating MIF-expressing lymphocytes in the recipients of BM and SP from WT-BALB/c mice, while the bile ducts were not destroyed even by infiltrating MIF-deficient lymphocytes in the recipients of BM and SP from MIF KO mice. Therefore, these findings suggest that MIF has an effect on the development of aGVHD in a murine model of allogeneic stem cell transplantation.
Toubai
Tomomi
T
Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. ttoubai@hkg.odn.ne.jp
Tanaka
Junji
J
Nishihira
Jun
J
Ohkawara
Tatsuya
T
Hirate
Daisuke
D
Kondo
Nobuo
N
Tone
Somako
S
Shono
Yusuke
Y
Ibata
Makoto
M
Sugita
Junichi
J
Kato
Naoko
N
Miura
Yoko
Y
Iwao
Noriaki
N
Ota
Shuichi
S
Imamura
Masahiro
M
D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013997:Time Factors; D014184:Transplantation, Homologous
D008263:Macrophage Migration-Inhibitory Factors