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 cou nts, and enhances and primes many neutrophil functions, implicating a role for this growth factor in host defence. This study investigated w hether G-CSF is able to directly influence the transendothelial migrat ion of neutrophils, and how such effects might be related to other eff ects on neutrophil adhesive properties. G-CSF, like GM-CSF, increased surface levels of the adhesive receptor, CD11b/CD18, but down-regulate d 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 significan t enhancement of neutrophil transmigration across unstimulated endothe lium in vitro. When used at an optimal concentration of 100 ng/ml, G-C SF increased, neutrophil migration to 217+/-19% of baseline levels (P< 0.001, n=10). This effect was similar to that preciously demonstrated for GM-CSF which increased migration to 271+/-40%, P<0.001, n=12). G-C SF-induced transmigration, like GM-CSF induced migration, was independ ent of concentration gradients, suggesting that these are not simply c hemotactic effects. G-CSF differs from GM-CSF, however, in that althou gh GM-CSF inhibited neutrophil migration across IL-1-activated endothe lium (33+/-8% inhibition, n=6, P<0.01), G-CSF had no effect on neutrop hil 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 cel l movement across inflamed endothelium. These results suggest that G-C SF is able to influence neutrophil recruitment into local infective si tes. and, further, that G-CSF mobilized cells would be competent to mi grate into tissues in response to inflammatory stimuli.