Buisman A M, Van Zwet T L, Langermans J A, Geertsma M F, Leenen P J, van Furth R
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Immunology. 1999 Aug;97(4):601-10. doi: 10.1046/j.1365-2567.1999.00835.x.
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.
在本研究中，评估了用粒细胞集落刺激因子（G-CSF）治疗对粒细胞减少小鼠（无论是否感染金黄色葡萄球菌）骨髓细胞组成和循环白细胞数量的影响。使用两种单克隆抗体，通过二维流式细胞术可以对骨髓中六个形态学上不同的细胞群体进行表征和定量。粒细胞减少是由环磷酰胺或亚致死剂量照射诱导的。环磷酰胺主要影响骨髓中分裂细胞的后期阶段，导致粒细胞、单核细胞、淋巴细胞和髓母细胞数量减少。给环磷酰胺处理的小鼠施用G-CSF可增加骨髓中早期母细胞、髓母细胞和粒细胞的数量，这表明这种生长因子刺激了这些细胞在骨髓中的增殖。在环磷酰胺处理的小鼠感染期间，髓母细胞数量增加。然而，当在环磷酰胺和G-CSF处理的小鼠中诱导感染时，与未感染的类似处理小鼠相比，骨髓细胞的增殖没有变化。亚致死剂量照射影响所有骨髓细胞群体，包括早期母细胞。对受照射小鼠进行G-CSF治疗仅略微增加了髓母细胞的数量，而受照射小鼠无论是否接受G-CSF治疗，感染均不影响骨髓细胞数量。总之，这些研究表明，照射对骨髓中早期母细胞和髓母细胞的影响比环磷酰胺治疗更严重。照射可能使骨髓中对G-CSF有反应的细胞耗竭，而环磷酰胺使对G-CSF有反应的细胞得以保留，从而使环磷酰胺治疗后G-CSF介导的恢复增强。只有在这些小鼠中，骨髓恢复后，在细菌感染期间会有大量成熟粒细胞及其带状形式从骨髓动员到循环中。
