EFFECTS OF IN-VIVO ADMINISTRATION OF G-CSF ON NEUTROPHIL AND EOSINOPHIL ADHESION

The effect in vivo of G-CSF on neutrophil and eosinophil adhesion was studied after subcutaneous administration to six healthy individuals o f human recombinant glycosylated G-CSF (lenograstim) (3 mu g/kg) for 6 consecutive days. Basal adhesion and adhesion to E-selectin, VCAM-1 a nd ICAM-1 of neutrophil and eosinophil granulocytes were measured sele ctively. During G-CSF administration neutrophil basal adhesion increas ed from 7.4 +/- 3.9% (mean +/- SD) to 55.8 +/- 12.9% and 23.2 +/- 4.4% , 4 and 7 d, respectively, after start of the administration. At the s ame 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 me asured in the presence of Mn2+, which increases the functional activit y of integrins, an even higher increase of neutrophil and eosinophil b asal adhesion was noted 4 and 7 d, respectively after start of G-CSF a dministration. In parallel with the enhanced basal adhesion neutrophil adhesion to E-selectin and ICAM-1 and eosinophil adhesion to E-select in, VCAM-1 and ICAM-1 were significantly (P < 0.05) increased after 4 d 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/mi TNF alpha significantly increased neutrophil and eosinophil basal adh esion 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 func tional capacity of beta(1)- and beta(2)-integrins. The induction of in creased levels of TNF alpha might be one mechanism behind the in vivo effect of G-CSF administration.