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 7 d, 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 7 d, 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 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/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.

Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF

“…G-CSF up-regulates the expression of antitumor neutrophil markers, such as ICAM1 and TNF-α, and promotes the formation of neutrophil extracellular traps (NETs) (33,35,36). As In contrast, an antitumor effect was observed when RT was delivered in limited fractions (45).…”

Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia

“…Apart from modulating the production and mobilization of PMNs in the bone marrow, G-CSF may affect the surface expression of adhesion molecules and Fc-g receptors on the PMNs [30,31]. In this respect, the increased expression of CD16 and CD62L on the circulating PMNs from CF + P patients after antibiotic treatment may be caused by the reduced concentration of G-CSF in the sera.…”

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

“…RhG-CSF-induced effects on neutrophils are well described [5, 15-17]. RhG-CSF stimulates the proliferation of myeloid precursors, accelerates neutrophil release from the bone marrow.…”