Effects of recombinant human macrophage colony-stimulating factor on proliferation, differentiation and survival of Kupffer cells in the liver of adult mice.
OBJECTIVE
To investigate the effects of macrophage colony-stimulating factor (M-CSF) on the proliferation, differentiation and survival of Kupffer cells in the liver of adult mice.


METHODS
By the combined method of autoradiography with [3H]thymidine and immunohistochemistry using a monoclonal antibody against mouse macrophages (F4/80 or BM8), the labeling rate of [3H]thymidine in macrophages within the liver sinusoids was examined at various intervals after single flash labeling with [3H]thymidine in adult mice with or without daily administration of recombinant human M-CSF.


RESULTS
A minor population of Kupffer cells (about 2%) possessed proliferative capacity under a normal steady state condition. With time after flash labeling, the influx of monocytes and their differentiation into macrophages were demonstrated in the liver, and their labeling rate returned to the baseline level one week later. Afterward, the labeling rate of Kupffer cells was maintained at the baseline level until the end of five weeks. Administration of M-CSF enhanced the proliferative capacity of Kupffer cells, increased the number of macrophages and delayed the time of peaking. However, it did not prolong the survival of Kupffer cells.


CONCLUSIONS
In normal mice, Kupffer cells can survive for at least five weeks. Daily M-CSF administration induces the increased number and proliferative capacity of Kupffer cells.
Miyakawa
K
K
Second Department of Pathology, Kumamoto University School of Medicine, Japan.
Myint
Y Y
YY
Takahashi
K
K
D000818:Animals; D001345:Autoradiography; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D007728:Kupffer Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D013936:Thymidine