Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor

A. Falanga, M. Marchetti, V. Evangelista, S. Manarini, E. Oldani, S. Giovanelli, M. Galbusera, C. Cerletti, T. Barbui

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Granulocyte colony-stimulating factor (G-CSF) enhances neutrophil functions in vitro and in vivo. It is known that neutrophil-derived products can alter the hemostatic balance. To understand whether polymorphonuclear leukocyte (PMN) activation, measured as PMN degranulation and phenotypical change, may be associated to hemostatic alterations in vivo, we have studied the effect of recombinant human G-CSF (rHuG-CSF) administration on leukocyte parameters and hemostatic variables in healthy donors of hematopoietic progenitor cells (HPCs). Twenty-six consecutive healthy donors receiving 10 μg/kg/d rHuG-CSF subcutaneously for 5 to 7 days to mobilize HPCs for allogeneic transplants were included in the study. All of them responded to rHuG-CSF with a significant white blood cell count increase. Blood samples were drawn before therapy on days 2 and 5 and 1 week after stopping rHuG-CSF treatment. The following parameters were evaluated: (1) PMN activation parameters, ie, surface CD11b/CD18 antigen expression, plasma elastase antigen levels and cellular elastase activity; (2) plasma markers of endothelium activation, ie, thrombomodulin (TM) and yon Willebrand factor (vWF) antigens; (3) plasma markers of blood coagulation activation, ie, F1+2, TAT complex, D-dimer; and (4) mononuclear cell (MNC) procoagulant activity (PCA) expression. The results show that, after starting rHuG-CSF, an in vivo PMN activation occurred, as demonstrated by the significant increment of surface CD11b/CD18 and plasma elastase antigen levels. Moreover, PMN cellular elastase activity, which was significantly increased at 1 day of treatment, returned to baseline at day 5 to 6, in correspondence with the elastase antigen peak in the circulation. This change was accompanied by a parallel significant increase in plasma levels of the two endothelial and the three coagulation markers. The PCA generated in vitro by unstimulated MNC isolated from rHuG-CSF-treated subjects was not different from that of control cells from untreated subjects. However, endotoxin-stimulated MNC isolated from on- treatment individuals produced significantly more PCA compared with both baseline and control samples. All of the parameters were decreased or normal 1 week after stopping treatment. These data show that rHuG-CSF induces PMN activation and transiently affects some hemostatic variables in healthy HPC donor subjects. The clinical significance of these findings remains to be established.

Original languageEnglish
Pages (from-to)2506-2514
Number of pages9
JournalBlood
Volume93
Issue number8
Publication statusPublished - Apr 15 1999

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Neutrophil Activation
Granulocyte Colony-Stimulating Factor
Hemostatics
Chemical activation
Pancreatic Elastase
Neutrophils
Plasmas
Hematopoietic Stem Cells
Antigens
Blood
Coagulation
CD18 Antigens
CD11b Antigens
Cells
Thrombomodulin
Leukocyte Elastase
Transplants
Blood Coagulation
Surface Antigens
Leukocyte Count

ASJC Scopus subject areas

  • Hematology

Cite this

Falanga, A., Marchetti, M., Evangelista, V., Manarini, S., Oldani, E., Giovanelli, S., ... Barbui, T. (1999). Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. Blood, 93(8), 2506-2514.

Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. / Falanga, A.; Marchetti, M.; Evangelista, V.; Manarini, S.; Oldani, E.; Giovanelli, S.; Galbusera, M.; Cerletti, C.; Barbui, T.

In: Blood, Vol. 93, No. 8, 15.04.1999, p. 2506-2514.

Research output: Contribution to journalArticle

Falanga, A, Marchetti, M, Evangelista, V, Manarini, S, Oldani, E, Giovanelli, S, Galbusera, M, Cerletti, C & Barbui, T 1999, 'Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor', Blood, vol. 93, no. 8, pp. 2506-2514.
Falanga A, Marchetti M, Evangelista V, Manarini S, Oldani E, Giovanelli S et al. Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. Blood. 1999 Apr 15;93(8):2506-2514.
Falanga, A. ; Marchetti, M. ; Evangelista, V. ; Manarini, S. ; Oldani, E. ; Giovanelli, S. ; Galbusera, M. ; Cerletti, C. ; Barbui, T. / Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. In: Blood. 1999 ; Vol. 93, No. 8. pp. 2506-2514.
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