title: Mast cell development and biostresses: different stromal responses in bone marrow and spleen after treatment of myeloablater, 5-fluorouracil, and inflammatory stressor, lipopolysaccharide.
abstract: Mast-cell-development in the bone-marrow (BM) and the spleen is restrictedly controlled by stromal-cells which produce positive-regulators such as stem cell factor (SCF), and negative-regulators such as transforming growth factor-β (TGF-β). How the balance between positive- and negative-regulation is achieved or maintained by stromal-cells is not well understood. We intravenously injected 5-fluorouracil (5-FU) and lipopolysaccharide (LPS) into C3H/HeN mice to disrupt mast-cell-development in order to reveal mechanisms of mast-cell-regulation. 5-FU treatment induces a rapid decrease in the number of mast-cell-progenitor (colony-forming unit (CFU)-mast) cells in the BM and spleen, followed by rapid recovery of CFU-mast numbers. Expression of the SCF gene is one-fiftieth the level of that of TGF-β during the steady-state in BM and spleen. After 5-FU treatment, SCF mRNA levels in the BM markedly increased, approaching TGF-β mRNA levels, whereas SCF levels in the spleen showed limited oscillations whose increases paralleled those in TGF-β levels. In contrast, LPS treatment induces a rapid decrease in CFU-mast number in the BM and a rapid increase in of CFU-mast number in the spleen. After LPS treatment, SCF mRNA levels in the BM markedly decreased, whereas SCF levels in the spleen remained unchanged. These results suggest that regulation of mast-cell-development is dominated by negative-signals in the BM and spleen during the steady-state, and, under biostress-conditions such as 5-FU and LPS treatment, the balance between positive- and negative-regulation can be changed in the BM but not in the spleen. The difference in the regulation of mast-cell-development in the BM versus the spleen probably reflects the different roles of tissue-specific stromal-cells.
authors.affiliation: Department of Functional Morphology, School of Medicine, Nihon University, Tokyo 173–8610, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Hokari
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Harada
authors.forename: Hideki
authors.initials: H
authors.lastname: Oshima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli; D005260:Female; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D055014:Granulocyte-Macrophage Progenitor Cells / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology; D013997:Time Factors
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D005472:Fluorouracil