Differential effects of granulocyte- and granulocyte-macrophage colony-stimulating factors (G- and GM-CSF) on neutrophil adhesion in vitro and in vivo.
A direct comparison of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) effects on neutrophil adhesiveness has been carried out. In vitro, GM-CSF and G-CSF upregulate neutrophil CD11b to a similar degree (to 227 +/- 69%, and 232 +/- 70% of control cells, respectively, p < 0.0005), but GM-CSF is more effective in downregulating neutrophil leucocyte adhesion molecule-1 (LAM-1), reducing levels to 33 +/- 4% (p < 0.0005), while G-CSF causes a fall to only 65 +/- 17% (p < 0.005) of control. The concentration of GM-CSF needed to achieve maximal activity is at least one log less than that of G-CSF. In vivo, both GM-CSF and G-CSF upregulate neutrophil CD11b (to 296 +/- 45% and 370 +/- 150%, respectively of baseline), but surface levels of LAM-1 on circulating cells are unchanged. GM-CSF increased neutrophil adhesion to cultured human endothelium in vitro (from 9.3 +/- 0.7% to 15.4 +/- 1.3%, p < 0.0005, n = 10), while G-CSF was without effect. In vivo, both GM-CSF and G-CSF produce a transient leucopenia, but recovery of peripheral counts occurs much earlier (by 60 minutes) with G-CSF, than with GM-CSF (only 50% of cells have demarginated at 120 min). GM-CSF appears to be greater proadhesive agonist for neutrophils than G-CSF.
D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D018845:CD11 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D006689:Hodgkin Disease / Q000097:blood / Q000628:therapy*; D066298:In Vitro Techniques; D007700:Kinetics; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014182:Transplantation, Autologous
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018845:CD11 Antigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor