Granulocyte-macrophage colony-stimulating factor enhances exudation of neutrophils to sites of inflammatory challenge in vivo.
Priming of neutrophil oxidative responses by granulocyte-macrophage colony-stimulating factor (GM-CSF) has been well documented, but its inhibitory effect on chemotaxis has led to concerns that its therapeutic administration may compromise neutrophil emigration to sites of infection and inflammation. We developed a murine model to determine the biodistribution kinetics of [111In] labeled neutrophils and used this model to study the influence of recombinant GM-CSF on neutrophil influx into inflammatory sites. Murine neutrophils were harvested from the peritoneal exudate 3 h after the intraperitoneal injection of fluid thioglycollate medium, radiolabeled with [111In]tropolonate, and resuspended in 10% acid/citrate/dextrose: 90% Hanks' balanced salt solution (without Ca2+ and Mg2+) at pH 6.5 for re-injection. To assess the in vivo effect of GM-CSF, 22 mice were injected intravenously with labeled neutrophils 1 h prior to intraperitoneal challenge with thioglycollate or saline. Half of the mice also received 2.0 micrograms of recombinant murine GM-CSF intravenously at the time of injection of labeled cells. GM-CSF had no influence on the influx of labeled cells to the peritoneum of animals that received i.p. saline, but increased by nearly 50% the cellular migration elicited by i.p. injection of thioglycollate. We conclude that GM-CSF does not impair, but rather enhances, the ability of circulating neutrophils to respond to thioglycollate-induced inflammation in vivo. The model we describe provides a useful and controllable method to investigate the effects of GM-CSF and other cytokines on the biodistribution kinetics and emigration of neutrophils in vivo.
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BH
Department of Radiology, Indiana University School of Medicine, Indianapolis 46223.
English
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D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007249:Inflammation / Q000209:etiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor