title: Age-dependent abnormalities of hematopoietic stem cells in (NZW x BXSB)F1 mice.
abstract: The (NZW x BXSB)F1 (W/BF1) mouse is known as an autoimmune-prone strain which develops lupus nephritis, thrombocytopenia due to platelet-specific autoantibodies, leukocytosis, and myocardial infarction. In this experiment, we investigated the age-dependent abnormalities of the hematopoietic stem cells (HSCs) and hematopoiesis in this mouse. White blood cell counts (especially Mac-1- or Gr-1-positive cells) in the peripheral blood of 12-week-old W/BF1 mice increased in comparison with those of four-week-old W/BF1 or normal mice. To investigate whether the abnormal hematopoiesis can be attributed to the HSCs of W/BF1 mice, colony-forming unit in spleen (CFU-S) and colony-forming unit in culture (CFU-C) assays were performed. Day 12 CFU-S counts of 12-week-old W/BF1 mice significantly increased in comparison with those of four-week-old W/BF1 mice or normal mice. In the CFU-C assay, CFU-GEMM and CFU-GM counts in 12-week-old W/BF1 mice increased in comparison with those of four-week-old W/BF1 or control mice. The bone marrow cells (BMCs) from 12-week-old W/BF1 mice showed a high level of G-CSF and a low level of GM-CSF in mRNA expression. To examine the effect of HSCs from 12-week-old W/BF1 mice on the onset of autoimmune diseases and the abnormal hematopoiesis, T- and B-cell-depleted BMCs of four-week-old or 12-week-old W/BF1 mice were transplanted to C3H mice. Recipient C3H mice that had received the BMCs from 12-week-old W/BF1 mice showed an earlier onset of autoimmune diseases and a shorter survival rate than those that had received the BMCs from four-week-old W/BF1 mice. These data suggest that the HSCs from 12-week-old W/BF1 mice showing the symptoms of autoimmune diseases have the capacity to induce autoimmune diseases earlier than the HSCs from four-week-old W/BF1 mice.
authors.affiliation: First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sugihara
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: M
authors.initials: M
authors.lastname: Inaba
authors.forename: H
authors.initials: H
authors.lastname: Hisha
authors.forename: K
authors.initials: K
authors.lastname: Sugiura
authors.forename: S
authors.initials: S
authors.lastname: Miyashima
authors.forename: Y
authors.initials: Y
authors.lastname: Amoh
authors.forename: S
authors.initials: S
authors.lastname: Taketani
authors.forename: H
authors.initials: H
authors.lastname: Oyaizu
authors.forename: K
authors.initials: K
authors.lastname: Ikebukuro
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
authors.forename: H
authors.initials: H
authors.lastname: Genba
authors.forename: T
authors.initials: T
authors.lastname: Horio
authors.forename: S
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D017668:Age of Onset; D000375:Aging / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006410:Hematopoiesis / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000473:pathology*; D007958:Leukocyte Count; D007964:Leukocytosis / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008181:Lupus Nephritis / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008814:Mice, Inbred NZB; D010976:Platelet Count; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000401:mortality / Q000473:pathology* / Q000628:therapy
chemical_list: D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor