Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.
To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage.
Serizawa
I
I
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd, Takasaki, Gunma, Japan. i-serizawa@kirin.co.jp
Amano
K
K
Ishii
H
H
Ichikawa
T
T
Kusaka
M
M
Taguchi
T
T
Kiyokawa
N
N
Fujimoto
J
J
D000818:Animals; D003643:Death; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology*; D009928:Organ Specificity
D016179:Granulocyte Colony-Stimulating Factor