Ex vivo neutrophil function in response to three different doses of glycosylated rHuG‐CSF (Lenograstim)

Abstract

Summary. Granulocyte colony-stimulating factor (G-CSF) is being considered as adjuvant treatment for infections in non-neutropenic patients. Normal healthy donors were given rHuG-CSF (Lenograstim) at 2 . 5, 5 . 0 and 7 . 5 g/kg subcutaneously daily for 5 d. Polymorphonuclear leucocyte (PMN) function tests were carried out on peripheral blood PMN before the first injection and at 24 h and 96 h. Circulating PMN levels were also measured at these time intervals and found to be significantly increased with all doses by 24 and 96 h. Investigation of cell surface antigen expression revealed no changes in 2 integrin (CD11b/ CD18) expression. L-selectin (CD62L) expression was reduced with all doses by 96 h, this being significant with the 7 . 5 g/kg dose. FcRI (CD64) levels were significantly up-regulated with the 7 . 5 g/kg dose by 96 h whereas FcRIII (CD16) expression was found to be reduced during G-CSF treatment. Superoxide anion production was significantly increased in response to N-formylmethionylleucylphenylalanine (FMLP) and opsonized Staphylococcus epidermidis stimulation at 24 h and 96 h with the 5 . 0 and 7 . 5 g/kg doses. The initial rate of phagocytosis (0-2 min) appeared to have increased with the 7 . 5 and 5 . 0 g/kg doses at 96 and 24 h compared with PMN responses pretreatment, although these increases were not statistically significant. These results show that G-CSF enhances the functional responses of PMN stimulated by physiological agonists and may help in the treatment of infections.

Phase I Study of Rituximab-CHOP Regimen in Combination with Granulocyte Colony-Stimulating Factor in Patients with Follicular Lymphoma

“…The high-affinity receptor for Fc␥RI is an early myeloid differentiation marker that is lost at the metamyelocyte stage during normal final maturation of PMN cells and is therefore not expressed on mature cells. It has been demonstrated that G-CSF acts on committed myeloid progenitor cells rather than on mature cells and that G-CSF strongly induces Fc␥RI expression in the precursor cells, resulting in Fc␥RI-positive mature PMN cells (11). Fc␥RI appeared to be the main Fc␥R involved in neutrophil-mediated ADCC assays.…”

“…Taken together, these studies support that Fc␥R-dependent mechanisms play a role in the effects of rituximab treatment. In vitro studies have confirmed that granulocyte colony-stimulating factor (G-CSF) up-regulates the expression of Fc␥RI (CD64) on polymorphonuclear (PMN) cells, which play an important role in exerting ADCC activities (10,11), and it has been considered that G-CSF augments the effects of rituximab. In addition, experiments using a bispecific antibody (Fc␣RI ϫ CD20) have confirmed that G-CSF enhances cytotoxic activities regulated by Fc␣RI by increasing the number of effector cells, although it does not up-regulate Fc␣RI (CD89) expression (12).…”

Contribution of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) use in current cancer treatment: review of clinical data

“…Chemotactic and phagocytic functions were normal or even enhanced, either in in vitro [31] or in vivo [32][33][34] studies. Furthermore, lenograstim should stimulate in vivo infection resistance and act in synergy with antibiotics [32,34,35].…”

“…Chemotactic and phagocytic functions were normal or even enhanced, either in in vitro [31] or in vivo [32][33][34] studies. Furthermore, lenograstim should stimulate in vivo infection resistance and act in synergy with antibiotics [32,34,35]. Similar to other haematopoietic growth factors, stimulating properties of lenograstim on human endothelial cells were reported in vitro and in vivo [36][37][38].…”

Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b

“…Similar stimulus-dependent responses to rhG-CSF therapy have been reported previously, and several possible mechanisms have been proposed. [19][20][21][22][23][24][25] The rhG-CSF therapy may modulate signal transduction pathways linked to receptors rather than directly altering components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The enhanced response to fMLP, but not to PMA, a direct activator of protein kinase C, indicates an alteration in signal transduction preceding protein kinase C activation.…”