Role of Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor in the Development of an Acute Neutrophil Inflammatory Response in Mice

Abstract

The intraperitoneal injection into mice of casein preparations containing bacteria induced a rapid accumulation of neutrophils within 3 hours due to selective release of mature cells from the bone marrow. Significant increases in the concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) occurred in the peritoneal cavity during the process, but the intraperitoneal injection of neither CSF induced a significant accumulation of neutrophils and the coinjection of G-CSF and casein failed to enhance the neutrophil response. The lack of involvement of either CSF in the neutrophil migration was confirmed by the development of typical neutrophil exudates when casein was injected into mice with inactivation of the genes encoding GM-CSF, G-CSF, or the beta-common chain of the GM-CSF receptor. However, preinjection of G-CSF increased the number of marrow neutrophils available for migration and did result in increased numbers of neutrophils in the peritoneal cavity after casein injection. Typical eosinophil inflammatory responses to the injection of casein or thioglycollate occurred in GM-CSF -/ -mice but not in beta c -/- mice, suggesting that interleukin-5 was necessary for this response.