Altered bone marrow cell sensitivity in the lupus-prone NZB/W mouse: Regulation of CFU-GM colony formation by estrogen, tamoxifen and thrombopoietin

S. M. Aronica, A. Dozier, P. Fanti, M. Nazareth

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Estrogen is thought to contribute to the onset of systemic lupus erythematosus (SLE) in women through mechanisms that are not completely understood. Although estrogen serves as a negative regulator in normal hematopoietic development, little research has been conducted examining alteration in hematopoietic development triggered by estrogen in lupus-susceptible individuals. We examined whether estrogen and other factors could influence colony formation of bone marrow cells obtained from normal and lupus-susceptible mice. Bone marrow cells isolated from New Zealand Black (NZB) and lupus-prone New Zealand Black and New Zealand White cross (NZB/W) mice were cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) alone or in combination with estrogen, thrombopoietin (TPO), tamoxifen, estrogen and TPO, or estrogen and tamoxifen, and plated in methylcellulose culture medium. Plates were scored for the number of CFU-GM (colony forming unit granulocyte-macrophage) colonies after 6 d in culture. For females of both mouse strains, estrogen significantly decreased (P < 0.05) the number of GM colonies. Co-treatment of NZB/W cells, but not NZB cells, with TPO or tamoxifen released the suppressive action of estrogen (P < 0.05). In contrast, while estrogen did suppress colony formation from cells of NZB/W males (P < 0.05), neither TPO nor tamoxifen reversed this effect. Our results indicate that the sensitivity of bone marrow cells isolated from both female and male NZB/W lupus-prone mice to hormones/growth factors is qualitatively different from cells of NZB mice, and suggest that hematopoietic alterations at the level of the bone marrow may be related to the pathogenesis of SLE.

Original languageEnglish (US)
Pages (from-to)271-277
Number of pages7
JournalLupus
Volume9
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • CFU-GM
  • Estrogen
  • Hematopoiesis
  • NZB/W
  • SLE

ASJC Scopus subject areas

  • Rheumatology

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