Effects of alpha-galactosylceramides on bone marrow cells in vitro and hematopoiesis in vivo.
We found that AGL-517, an alpha-galactosylceramide (alpha-GalCer), possesses potent radioprotective activities against mice irradiated with 9 Gy of X-ray in contrast to its having no effect on mice irradiated with 10 Gy of X-ray. The result suggested the possibility that alpha-GalCers protect mice from bone marrow death. To examine this possibility, we examined the effects of two kinds of alpha- and beta-GalCers on counts of platelets (PLT) and white blood cells (WBC) in the peripheral blood of normal mice and mice irradiated in a whole body with 5 Gy of X-ray. alpha-GalCers significantly increased the PLT and WBC counts of both mice in comparison with the vehicle-treated group, and their potencies were stronger than those of their beta-types. Furthermore, we evaluated the in vitro bone marrow cell-proliferation stimulatory activities of four kinds of GalCers, and found that alpha-GalCers show stronger stimulatory effects than beta-types. These results demonstrate that the alpha-configuration of GalCers plays an important role in the manifestation of the above-mentioned activities of GalCers. The results also suggest that alpha-GalCers may be useful as hematopoietic stimulators as well as radioprotective agents.
Motoki
K
K
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Morita
M
M
Kobayashi
E
E
Uchida
T
T
Fukushima
H
H
Koezuka
Y
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005699:Galactosylceramides / Q000737:chemistry / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010976:Platelet Count / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013268:Stimulation, Chemical; D013534:Survival; D014916:Whole-Body Irradiation
D005699:Galactosylceramides; D011837:Radiation-Protective Agents