Granulocyte colony-stimulating factor (G-CSF) increases neutrophil migration across vascular endothelium independent of an effect on adhesion: comparison with granulocyte-macrophage colony-stimulating factor (GM-CSF).

Granulocyte colony-stimulating factor (G-CSF) increases neutrophil counts, and enhances and primes many neutrophil functions, implicating a role for this growth factor in host defence. This study investigated whether G-CSF is able to directly influence the transendothelial migration of neutrophils, and how such effects might be related to other effects on neutrophil adhesive properties. G-CSF, like GM-CSF, increased surface levels of the adhesive receptor, CD11b/CD18, but down-regulated L-selectin expression on neutrophils. Unlike GM-CSF, however, G-CSF had no effect on neutrophil adhesion to endothelium. Despite the lack of effect on neutrophil adhesion, G-CSF was able to produce significant enhancement of neutrophil transmigration across unstimulated endothelium in vitro. When used at an optimal concentration of 100 ng/ml, G-CSF increased neutrophil migration to 217 +/- 19% of baseline levels (P < 0.001, n = 10). This effect was similar to that previously demonstrated for GM-CSF (which increased migration to 271 +/- 40%, P < 0.001, n = 12). G-CSF-induced transmigration, like GM-CSF induced migration, was independent of concentration gradients, suggesting that these are not simply chemotactic effects. G-CSF differs from GM-CSF, however, in that although GM-CSF inhibited neutrophil migration across IL-1-activated endothelium (33 +/- 8% inhibition, n = 6, P < 0.01), G-CSF had no effect on neutrophil migration across IL-1 activated endothelium. Hence G-CSF, despite having no effect on neutrophil adhesion to endothelium, is a powerful stimulator of transmigration, and, unlike GM-CSF, does not inhibit cell movement across inflamed endothelium. These results suggest that G-CSF is able to influence neutrophil recruitment into local infective sites, and, further, that G-CSF mobilized cells would be competent to migrate into tissues in response to inflammatory stimuli.