Glycosylated or non-glycosylated G-CSF differently influence human granulocyte functions through RhoA.
Granulocyte function may be altered after in vivo G-CSF administration and this has been related to both an immaturity of mobilized cells and to a defect in F-actin polymerization. In this paper we show that in resting Filgrastim (non-glycosylated G-CSF)-pulsed cells, F-actin polymerization, membrane-linked RhoA and cell polarization are enhanced compared to those found in resting Lenograstim (glycosylated G-CSF)-cells. The basal hyper-activation of RhoA could be responsible for the morphological and functional modifications of Filgrastim-mobilized cells. Moreover, Filgrastim-mobilized cells, but not Lenograstim-mobilized cells, are unable to correctly respond to LPS stimulation, as demonstrated by minor further RhoA activation and cell elongation.
Mattii
Letizia
L
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
Azzarà
Antonio
A
Fazzi
Rita
R
Carulli
Giovanni
G
Chimenti
Massimo
M
Cecconi
Nadia
N
Galimberti
Sara
S
Petrini
Mario
M
D000199:Actins / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D000069585:Filgrastim; D006031:Glycosylation; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D000078224:Lenograstim; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D036102:Peripheral Blood Stem Cell Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D012074:Remission Induction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism / Q000502:physiology*
D000199:Actins; D011994:Recombinant Proteins; C066737:RHOA protein, human; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D020742:rhoA GTP-Binding Protein; D000069585:Filgrastim