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Age-Dependent Abnormalities of Hematopoietic Stem Cells in (NZW x BXSB)F₁ Mice

^a First Department of Pathology;
^b Department of Dermatology;
^c Department of Orthopedic Surgery;
^d Third Department of Internal Medicine;
^e Department of Hygiene;
^f First Department of Internal Medicine;
^g Second Department of Surgery;
^h Second Department of Physiology, Kansai Medical Unversity, Moriguchi City, Osaka, Japan

Key Words. W/BF₁ mice • BMT • Leukocytosis • Cytokines • Stem cells • Autoimmune diseases

Correspondence: Dr. Susumu Ikehara, First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8606, Japan.

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.

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