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

Estrogen is thought to contribute to the onset of systemic lupus erythemato sus (SLE) in women through mechanisms that are not completely understood. A lthough estrogen serves as a negative regulator in normal hematopoietic dev elopment, little research has been conducted examining alteration in hemato poietic development triggered by estrogen in lupus-susceptible individuals. We examined whether estrogen and other factors could influence colony form ation of bone marrow cells obtained from normal and lupus-susceptible mice. Bone marrow cells isolated from New Zealand Black (NZB) and lupus-prone Ne w Zealand Black and New Zealand White cross (NZB/W) mice were cultured in t he presence of granulocyte-macrophage colony stimulating factor (GM-CSF) al one or in combination with estrogen, thrombopoietin (TPO), tamoxifen, estro gen and TPO, or estrogen and tamoxifen, and plated in methylcellulose cultu re 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 G M colonies. Go-treatment of NZB/W cells, but not NZB cells, with TPO or tam oxifen reversed 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 indica te that the sensitivity of bone marrow cells isolated from both female and male NZB/W lupus-prone mice to hormones/growth factors is qualitatively dif ferent from cells of NZB mice, and suggest that hematopoietic alterations a t the level of the bone marrow may be related to the pathogenesis of SLE.