Different effect of granulocyte colony-stimulating factor or bacterial infection on bone-marrow cells of cyclophosphamide-treated or irradiated mice

In the present study, the effect of treatment with granulocyte colony-stimu lating factor (G-CSF) on cellular composition of the bone marrow and the nu mber of circulating leucocytes of granulocytopenic mice, whether or not inf ected with Staphylococcus aureus, was assessed. With two monoclonal antibod ies, six morphologically distinct cell populations in the bone marrow could be characterised and quantitated by two-dimensional how cytometry. Granulo cytopenia was induced by cyclophosphamide or sublethal irradiation. Cycloph osphamide predominantly affected the later stages of dividing cells in the bone marrow resulting in a decrease in number of granulocytic cells, monocy tic cells, lymphoid cells and myeloid blasts. G-CSF administration to cyclo phosphamide-treated mice increased the number of early blasts, myeloid blas ts and granulocytic cells in the bone marrow, which indicates that this gro wth factor stimulates the proliferation of these cells in the bone marrow. During infection in cyclophosphamide-treated mice the number of myeloid bla sts increased. However, when an infection was induced in cyclophosphamide a nd G-CSF-treated mice, the proliferation of bone-marrow cells was not chang ed compared to that in noninfected similarly treated mice. Sublethal irradi ation affected all bane-marrow cell populations, including the early blasts . G-CSF-treatment of irradiated mice increased only the number of myeloid b lasts slightly, whereas an infection in irradiated mice, whether or not tre ated with G-CSF, did not affect the number of bone-marrow cells. Together, these studies demonstrated that irradiation affects the early blasts and my eloid blasts in the bone marrow more severely than treatment with cyclophos phamide. Irradiation probably depletes the bone marrow from G-CSF responsiv e cells, while cyclophosphamide spared G-CSF responsive cells, thus enablin g the enhanced G-CSF-mediated recovery after cyclophosphamide treatment. On ly in these mice, bone marrow recovery is followed by a strong mobilisation of mature granulocytes and their band forms from the bone marrow into the circulation during a bacterial infection.