title: Lipopolysaccharide reciprocally alters the stromal cell-regulated positive and negative balance between myelopoiesis and B lymphopoiesis in C57BL/6 mice.
abstract: Hematopoiesis in the bone marrow (BM) and spleen is controlled by stromal cells. Inflammation promotes myelopoiesis and simultaneously suppresses B lymphopoiesis. However, the role of the reciprocal regulation of myelopoiesis and B lymphopoiesis by stromal cells during inflammation is not fully understood. We investigated inflammation-induced alteration of hematopoietic regulation in lipopolysaccharide (LPS)-treated mice. C57BL/6 female mice were intravenously injected with a single, 5-µg dose of LPS, which induced a rapid decrease in the number of granulocyte-macrophage progenitors (colony-forming unit granulocyte-macrophage; CFU-GM) and B cell progenitors (CFU-preB) in BM. The CFU-GM count rapidly recovered, whereas the recovery of CFU-preB was delayed. LPS induced a marked increase in the number of CFU-GM but not in the number of CFU-preB in spleen. After LPS treatment, gene expression levels of positive regulators of myelopoiesis such as granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in BM and spleen were markedly upregulated whereas levels of positive regulators for B lymphopoiesis such as stromal cell-derived factor (SDF)-1, stem cell factor (SCF), and IL-7 remained unchanged. Meanwhile, the negative regulator of B lymphopoiesis tumor necrosis factor (TNF)-α was markedly up-regulated. The number of CFU-GM in S-phase in BM increased after LPS treatment, whereas the number of CFU-preB in S-phase decreased. These results suggest that LPS-activated stromal cells induce positive-dominant regulation of myelopoiesis and negative-dominant regulation of B lymphopoiesis, which facilitates emergency myelopoiesis during inflammation by suppressing B lymphopoiesis, thereby contributing to the host defense against infection.
authors.affiliation: Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taki
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Harada
authors.forename: Michiko
authors.initials: M
authors.lastname: Naito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hara
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055014:Granulocyte-Macrophage Progenitor Cells / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D038041:Lymphopoiesis / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000187:drug effects*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000502:physiology
chemical_list: D016207:Cytokines; C503133:Gr-1 protein, mouse; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine