Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion

Abstract

The effect in vivo of G-CSF on neutrophil and eosinophil adhesion was studied after subcutaneous administration to six healthy individuals of human recombinant glycosylated G-CSF (lenograstim) (3 μg/kg) for 6 consecutive days. Basal adhesion and adhesion to E-selectin, VCAM-1 and ICAM-1 of neutrophil and eosinophil granulocytes were measured selectively. During G- CSF administration neutrophil basal adhesion increased from 7.4 ± 3.9% (mean ± SD) to 55.8 ± 12.9% and 23.2 ± 4.4%, 4 and 7d, respectively, after start of the administration. At the same time points eosinophil basal adhesion increased from 7.1 ± 2.4% to 37.7 ± 6.1% and 13.1 ± 5.3%, respectively. When adhesion was measured in the presence of Mn2+, which increases the functional activity of integrins, an even higher increase of neutrophil and eosinophil basal adhesion was noted 4 and 7d, respectively, after start of G- CSF administration. In parallel with the enhanced basal adhesion neutrophil adhesion to E-selectin and ICAM-1 and eosinophil adhesion to E-selectin, VCAM-1 and ICAM-1 were significantly (P<0.05) increased after 4d of G-CSF administration as was neutrophil cell surface expression of CD11b and CD18. In vitro G-CSF induced minimal changes of granulocyte basal adhesion and inhibition of the adhesion to E-selectin. 10 ng/ml TNFα significantly increased neutrophil and eosinophil basal adhesion and adhesion to VCAM-1 and ICAM-1. In summary, administration of G-CSF to healthy subjects induced enhanced adhesion of neutrophil and eosinophil granulocytes, probably mediated by an increase of the functional capacity of β1- and β2- integrins. The induction of increased levels of TNFα might be one mechanism behind the in vivo effect of G-CSF administration.