Comparative study of the effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on generation and mobilization of neutrophils in cyclophosphamide-treated neutropenic mice

To examine the differential in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the recovery from neutropenia caused by chemotherapy, we directly compared the actions of these CSFs on neutrophil count in the bone marrow, spleen and peripheral blood of mice treated with an anticancer drug, cyclophosphamide (CPA). Both G-CSF and GM-CSF stimulated the generation of neutrophils in bone marrow, but GM-CSF is only about 1/20 as effective as G-CSF. Both CSFs also stimulated the release of the generated neutrophils therefrom. G-CSF mobilized the neutrophils into both the circulation pool and the marginal pool, and these neutrophils were able to migrate into the inflammatory site when stimulated by casein. On the other hand, GM-CSF mobilize the neutrophils into the marginal pool but not the circulation pool, and they were not able to migrate into the inflammatory site. These findings indicate that G-CSF physiologically plays an important role as a factor which stimulates neutrophil mobilization from bone marrow into circulation as well as neutrophil generation in the bone marrow.