A possible mechanism of increase in serum alkaline phosphatase activity in rats given granulocyte colony-stimulating factor.
Recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 1 to 300 micrograms/kg/day was administered intravenously to rats daily for 13 weeks. Serum alkaline phosphatase (ALP) activity increased dose-dependently with leukocytosis. Most of the increased leukocytes were segmented neutrophils, and neutrophil alkaline phosphatase (NAP) scores were elevated markedly. Serum ALP activity correlated very well with the segmented neutrophil counts, and the coefficient of correlation was more than 0.97 in both sexes. Pathological examinations revealed splenomegaly and a marked increase in neutrophils in the red pulp of the spleen. In the spleen, phagocytosis of neutrophils by macrophages was observed. These data indicate that the increased ALP was of neutrophil origin. Serum ALP activity may be increased by the direct release of ALP from the high number of neutrophils into the blood, or by the leakage of ALP into the blood mainly from the spleen where many neutrophils are pooled and destroyed by the macrophage system.
Kato
Y
Y
Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Yamaguchi, Japan.
Yamamoto
M
M
Ikegami
J
J
Okumura
S
S
Hara
T
T
Shuto
K
K
D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase