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-stimulating factor (G-CSF) on cellular composition of the bone marrow and the number of circulating leucocytes of granulocytopenic mice, whether or not infected with Staphylococcus aureus, was assessed. With two monoclonal antibodies, six morphologically distinct cell populations in the bone marrow could be characterised and quantitated by two-dimensional flow cytometry. Granulocytopenia was induced by cyclophosphamide or sublethal irradiation. Cyclophosphamide predominantly affected the later stages of dividing cells in the bone marrow resulting in a decrease in number of granulocytic cells, monocytic cells, lymphoid cells and myeloid blasts. G-CSF administration to cyclophosphamide-treated mice increased the number of early blasts, myeloid blasts and granulocytic cells in the bone marrow, which indicates that this growth factor stimulates the proliferation of these cells in the bone marrow. During infection in cyclophosphamide-treated mice the number of myeloid blasts increased. However, when an infection was induced in cyclophosphamide and G-CSF-treated mice, the proliferation of bone-marrow cells was not changed compared to that in noninfected similarly treated mice. Sublethal irradiation affected all bone-marrow cell populations, including the early blasts. G-CSF-treatment of irradiated mice increased only the number of myeloid blasts slightly, whereas an infection in irradiated mice, whether or not treated with G-CSF, did not affect the number of bone-marrow cells. Together, these studies demonstrated that irradiation affects the early blasts and myeloid blasts in the bone marrow more severely than treatment with cyclophosphamide. Irradiation probably depletes the bone marrow from G-CSF-responsive cells, while cyclophosphamide spared G-CSF responsive cells, thus enabling the enhanced G-CSF-mediated recovery after cyclophosphamide treatment. Only 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.
Buisman
A M
AM
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Van Zwet
T L
TL
Langermans
J A
JA
Geertsma
M F
MF
Leenen
P J
PJ
van Furth
R
R
D000380:Agranulocytosis / Q000139:chemically induced / Q000209:etiology / Q000628:therapy*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D001854:Bone Marrow Cells / Q000473:pathology*; D002452:Cell Count; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009894:Opportunistic Infections / Q000473:pathology*; D011833:Radiation Injuries, Experimental / Q000473:pathology; D013203:Staphylococcal Infections / Q000473:pathology; D014916:Whole-Body Irradiation / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide