title: Differential Regulation of Lympho-Myelopoiesis by Stromal Cells in the Early and Late Phases in BALB/c Mice Repeatedly Exposed to Lipopolysaccharide.
abstract: Chronic lipopolysaccharide (LPS) exposure to mice reduces the lymphoid compartment and skews the hematopoietic cell compartment toward myeloid-cells, which is considered to be a direct effect of LPS on hematopoietic stem cells. However, the effect of chronic LPS exposure on stromal-cells, which compose the hematopoietic microenvironment, has not been elucidated. Here, we investigated early- and late-phase effects of repeated LPS exposure on stromal-cells. During the early phase, when mice were treated with 5 or 25 µg LPS three times at weekly intervals, the numbers of myeloid-progenitor (colony forming unit-granulocyte macrophage (CFU-GM)) cells and B lymphoid-progenitor (CFU-preB) cells in the bone-marrow (BM) rapidly decreased after each treatment. The number of CFU-GM cells recovered from the initial decrease and then increased to levels higher than pretreatment levels, whereas the number of CFU-preB cells remained lower than pretreatment levels. In the BM, expression of genes for positive-regulators of myelopoiesis including granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-6 and negative-regulators of B lymphopoiesis including tumor necrosis factor (TNF)-α was up-regulated, whereas expression of positive-regulators of B lymphopoiesis including stromal cell-derived factor (SDF)-1, IL-7, and stem cell factor (SCF) was down-regulated. During the late phase, the number of CFU-preB cells remained lower than pretreatment levels 70 d after the first treatments with 5 and 25 µg LPS, whereas the number of CFU-GM cells returned to pretreatment levels. IL-7 gene expression in the BM remained down-regulated, whereas gene-expression levels of SDF-1 and SCF were restored. Thus, chronic LPS exposure may impair stromal-cell function, resulting in prolonged suppression of B lymphopoiesis, which may appear to be senescence similar to the hematological phenotype.
authors.affiliation: Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine.
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Harada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D038041:Lymphopoiesis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008807:Mice, Inbred BALB C; D038042:Myelopoiesis / Q000187:drug effects* / Q000502:physiology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides