Selective inhibition of resistance to hemopoietic allografts but not rejection to a natural killer cell sensitive tumor in transgenic mice for granulocyte colony stimulating factor.
Transplanted allogeneic marrow grafts often fail to engraft in a lethally irradiated host. Resistance to hemopoietic allograft is a complexed phenomenon involving multiple components. To study the involvement of a hemopoietic cytokine, which was known to play a role for stem cell function, we established lines of mice that were transgenic for human granulocyte colony-stimulating factor (hG-CSF). Elevated and constitutive expression was found in sera (1,041 +/- 242 pg/ml) of these transgenic mice regardless of their sexes and ages. Strong neutrophilic granulocytosis correlated with the elevated G-CSF activity in transgenic mice but not in littermate controls, establishing a functional expression of this cytokine. In lethally irradiated mice transgenic for G-CSF, infusion of fully allogeneic marrow cells induced donor-derived spleen colony. Growth of hemopoietic allografts appeared to be similar to those of syngeneic marrow cells, which indicates inhibition of resistance for allogeneic marrow grafts. Because of a positive correlation, involvement of natural killer (NK) cells in resistance of transplanted allografts has been suggested. Inocula of NK-sensitive lymphoma cells were, however, vigorously rejected in the G-CSF-transgenic mice. This observation indicates that G-CSF may play a role in engraftment of transplanted allogeneic marrow grafts and may represent a component of mechanisms of hemopoietic resistance. Furthermore, this result may be an indication that alloresistance and NK cells use different mechanisms to resist each target.
Kokai
Y
Y
Department of Pathology, Sapporo Medical University, School of Medicine, Japan.
Kimura
H
H
Matsuura
A
A
Fujimoto
J
J
D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured
D016179:Granulocyte Colony-Stimulating Factor