Predominant regeneration of B-cell lineage, instead of myeloid lineage, of the bone marrow after 1 Gy whole-body irradiation in mice: role of differential cytokine expression between B-cell stimulation by IL10, Flt3 ligand and IL7 and myeloid suppression by GM-CSF and SCF.
Irradiation of mice at doses of 1-1.5 Gy induced a predominant regeneration of the B-cell lineage but suppressed the regeneration of the myeloid lineage. The mechanisms underlying such reciprocal regulation of regeneration and the relationship between the two lineages remain unclear. Because the predominant regeneration of the B-cell lineage observed is considered to depend on the stromal cell function, and because the impairment of such stromal function may nullify such reciprocal responses, mouse models of senescent stromal cell impairment (SCI) and the less senescent stage of SCI (non-SCI) were compared to elucidate the mechanisms underlying the reciprocal regulation of both lineages after radiation exposure. In non-SCI mice irradiated with 1 Gy, the numbers of B-lymphocyte progenitor (CFU-preB) and granulocyte-macrophage progenitor (CFU-GM) cells in the bone marrow decreased rapidly during the first 24 h. Then the number of CFU-preB cells in the bone marrow promptly recovered from the nadir and exceeded the pretreatment level, whereas that of CFU-GM cells remained lower than the pretreatment level. The expression of genes encoding positive regulators of the B-lymphoid lineage [interleukin (IL)10, Flt3 ligand and IL7] was up-regulated; in contrast, expression of the positive regulators of the myeloid lineage [granulocyte macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF)] was down-regulated. In SCI mice irradiated with 1 Gy, the oscillatory changes in the numbers of femoral CFU-preB and CFU-GM cells and in the expression levels of cytokine genes were less marked than those in the non-SCI mice. These results thus imply that the reciprocal regeneration depends on the up-regulation of IL10, Flt3 ligand and IL7 expression and the down-regulation of GM-CSF and SCF expression in the bone marrow, possibly depending on the hematopoietic microenvironment.
Tsuboi
Isao
I
Department of Functional Morphology, Nihon University School of Medicine, Tokyo 173-8610, Japan. tsuboi@med.nihon-u.ac.jp
Hirabayashi
Yoko
Y
Harada
Tomonori
T
Hiramoto
Masaki
M
Kanno
Jun
J
Inoue
Tohru
T
Aizawa
Shin
S
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000528:radiation effects; D002454:Cell Differentiation / Q000276:immunology / Q000528:radiation effects; D019070:Cell Lineage / Q000528:radiation effects*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000528:radiation effects; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D014916:Whole-Body Irradiation
D016207:Cytokines; D007378:Interleukins; D008565:Membrane Proteins; C084881:flt3 ligand protein