In vivo administration of granulocyte colony-stimulating factor promotes neutrophil survival in vitro.
We recently showed that recombinant human granulocyte-colony stimulating factor (rhG-CSF) maintained the viability of human neutrophils in incubation for up to 72 hours. However, it is not known whether rhG-CSF can enhance neutrophil survival in in vivo situations. To clarify this issue, we investigated neutrophil survival in vitro following in vivo injection of rhG-CSF. Neutrophils were obtained from 4 pediatric patients with malignancies and healthy adult volunteers before and after rhG-CSF administration. Neutrophils obtained before rhG-CSF treatment started to undergo apoptosis after 24 h of incubation. In contrast, the survival of neutrophils drawn after rhG-CSF administration increased by approximately 24 h. Concomitantly, the appearance of typical ladder-like DNA fragmentation was delayed. Such an increase in neutrophil survival was inhibited by co-incubation with either H 7 (10 mumol/l) or H 8 (20 mumol/l), which worked as protein kinase C inhibitors. Although our study did not measure neutrophil survival in vivo directly, it provides us with further evidence that rhG-CSF may function to prolong neutrophil life expectancy in vivo.
Adachi
S
S
Department of Pediatrics, Kyoto University, Japan.
Kubota
M
M
Lin
Y W
YW
Okuda
A
A
Matsubara
K
K
Wakazono
Y
Y
Hirota
H
H
Kuwakado
K
K
Akiyama
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000293:Adolescent; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D007546:Isoquinolines; D010879:Piperazines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C