HEMATOPOIETIC AND LYMPHOPOIETIC RESPONSES IN HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) RECEPTOR TRANSGENIC MICE INJECTED WITH HUMAN GM-CSF

Using a clonal assay of bone marrow (BM) cells from transgenic mice (T g-mice) expressing the human granulocyte-macrophage colony-stimulating factor receptor (hGM-CSFR), we found in earlier studies that hGM-CSF alone supported the development not only of granulocyte-macrophage col onies, but also of erythrocytes, megakaryocytes, mast cells, blast cel ls, and mixed hematopoietic colonies, In this report, we evaluated the in vivo effects of hGM-CSF on hematopoietic and lymphopoietic respons es in the hGM-CSFR Tg-mice, Administration of this factor to Tg-mice r esulted in dose-dependent increases in numbers of reticulocytes and wh ite blood cells (WBCs) in the peripheral blood, Morphological analysis of WBCs showed that the numbers of all types of the cell, including n eutrophils, eosinophils, monocytes, and lymphocytes increased; the mos t remarkable being in lymphocytes that contained a number of large gra nular lymphocytes (LGLs) in addition to mature T and B cells. However, total cellularity of the BM of the Tg-mice decreased in a dose-depend ent manner when hGM-CSF was injected, In sharp contrast to the BM, spl eens of the Tg-mice were grossly enlarged. Although all types of blood cells and hematopoietic progenitors increased in the spleen, erythroi d cells and their progenitors showed the most significant increase. In creased numbers of megakaryocytes and LGLs were also observed in splee n and liver of the treated Tg-mice. Flow cytometric analysis showed th at LGLs expanded in Tg-mice expressed Mac-1(+)CD3(-)NK1.1(+). The thym us of Tg-mice treated with hGM-CSF exhibited a dose-dependent shrinkag e and a remarkable decrease in CD4(+)CD8(+) cells, Thus, hGM-CSF stimu lated not only myelopoiesis but also erythropoiesis and megakaryopoies is of hGM-CSFR Tg-mice in vivo, in accordance with our reported in vit ro findings. In addition, hGM-CSF affected the development of lymphoid cells, including natural killer cells of these Tg-mice. (C) 1997 by T he American Society of Hematology.