In vivo Administration of Granulocyte Colony-Stimulating Factor Increases the Surface Expression of Sialyl-Lewisx on Neutrophils in Healthy Volunteers

1998 ◽  
Vol 100 (4) ◽  
pp. 187-190 ◽  
Author(s):  
Akimichi Ohsaka ◽  
Katsu Saionji
Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2364-2371 ◽  
Author(s):  
KG Waddick ◽  
CW Song ◽  
L Souza ◽  
FM Uckun

The purpose of the present study was to evaluate and compare the in vivo radioprotective effects of pre-total body irradiation (TBI) conditioning with recombinant granulocyte colony-stimulating factor (rG- CSF) and recombinant granulocyte-macrophage CSF (rGM-CSF) in a large series of lethally and supralethally irradiated mice. Also analyzed were the radioprotective effects of simultaneous as well as sequential combinations of rG-CSF and rGM-CSF. Our findings in 1,180 mice provide direct evidence that in vivo administration of rG-CSF or rGM-CSF before TBI protects a significant fraction of mice from the lethal effects of LD100/30 TBI. At equivalent doses, rG-CSF displayed a more potent radioprotective activity than rGM-CSF. Not only was rG-CSF radioprotective at much smaller doses than rGM-CSF, the survival rate after lethal TBI was also significantly higher in mice receiving optimally radioprotective doses of rG-CSF as compared with mice receiving optimally radioprotective doses of rGM-CSF. Pretreatment of mice with rGM-CSF markedly attenuated the radioprotective affects of rG- CSF in lethally as well as supralethally irradiated mice. Pretreatment with rG-CSF followed by rGM-CSF was slightly more effective than rG-CSF alone in supralethally irradiated mice but not in lethally irradiated mice. Notably, marked differences among different strains of mice were noted regarding the optimally radioprotective doses of rG-CSF or rGM- CSF as well as probability of survival and median survival time after lethal or supralethal TBI. This report confirms and extends previous studies concerning the potential of cytokines in prevention or therapy of lethal radiation injury.


Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3885-3894 ◽  
Author(s):  
M de Haas ◽  
JM Kerst ◽  
CE van der Schoot ◽  
J Calafat ◽  
CE Hack ◽  
...  

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.


2009 ◽  
Vol 53 (3) ◽  
pp. 129-134 ◽  
Author(s):  
Souichi Adachi ◽  
Masaru Kubota ◽  
Ying Wei Lin ◽  
Akiro Okuda ◽  
Kousaku Matsubara ◽  
...  

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2364-2371 ◽  
Author(s):  
KG Waddick ◽  
CW Song ◽  
L Souza ◽  
FM Uckun

Abstract The purpose of the present study was to evaluate and compare the in vivo radioprotective effects of pre-total body irradiation (TBI) conditioning with recombinant granulocyte colony-stimulating factor (rG- CSF) and recombinant granulocyte-macrophage CSF (rGM-CSF) in a large series of lethally and supralethally irradiated mice. Also analyzed were the radioprotective effects of simultaneous as well as sequential combinations of rG-CSF and rGM-CSF. Our findings in 1,180 mice provide direct evidence that in vivo administration of rG-CSF or rGM-CSF before TBI protects a significant fraction of mice from the lethal effects of LD100/30 TBI. At equivalent doses, rG-CSF displayed a more potent radioprotective activity than rGM-CSF. Not only was rG-CSF radioprotective at much smaller doses than rGM-CSF, the survival rate after lethal TBI was also significantly higher in mice receiving optimally radioprotective doses of rG-CSF as compared with mice receiving optimally radioprotective doses of rGM-CSF. Pretreatment of mice with rGM-CSF markedly attenuated the radioprotective affects of rG- CSF in lethally as well as supralethally irradiated mice. Pretreatment with rG-CSF followed by rGM-CSF was slightly more effective than rG-CSF alone in supralethally irradiated mice but not in lethally irradiated mice. Notably, marked differences among different strains of mice were noted regarding the optimally radioprotective doses of rG-CSF or rGM- CSF as well as probability of survival and median survival time after lethal or supralethal TBI. This report confirms and extends previous studies concerning the potential of cytokines in prevention or therapy of lethal radiation injury.


Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2264-2269 ◽  
Author(s):  
BR Blazar ◽  
MB Widmer ◽  
D Cosman ◽  
HM Sassenfeld ◽  
DA Vallera

Abstract In vivo administration of human recombinant granulocyte colony- stimulating factor (rG-CSF) was evaluated for effects on survival, hematologic recovery, and engraftment in an allogeneic murine bone marrow transplantation (BMT) model involving T-cell depletion. Post-BMT recipients of continuous subcutaneous infusions of rG-CSF (n = 62) for 14 days had a significant survival advantage compared with post-BMT controls (n = 60) that received phosphate-buffered saline (PBS) infusions. Moreover, recipients of rG-CSF had significantly increased numbers of circulating leukocytes on days 7 and 14 post-BMT. Engraftment was not adversely affected. Administration of rG-CSF after transplantation of T-cell-depleted histoincompatible bone marrow benefits survival and leukocyte recovery without compromising engraftment.


Sign in / Sign up

Export Citation Format

Share Document