Vitamin A deficiency in mice causes a systemic expansion of myeloid cells.
To examine the role of retinoids in hematopoietic cell growth in vivo, we studied female SENCAR mice made vitamin A deficient by dietary restriction. Deficient mice exhibited a dramatic increase in myeloid cells in bone marrow, spleen, and peripheral blood. The abnormal expansion of myeloid cells was detected from an early stage of vitamin A deficiency and contrasted with essentially normal profiles of T and B lymphocytes. This abnormality was reversed on addition of retinoic acid to the vitamin A-deficient diet, indicating that the myeloid cell expansion is a direct result of retinoic acid deficiency. TUNEL analysis indicated that spontaneous apoptosis, a normal process in the life cycle of myeloid cells, was impaired in vitamin A-deficient mice, which may play a role in the increased myeloid cell population. Quantitative reverse transcriptase-polymerase chain reaction analysis of purified granulocytes showed that expression of not only RAR, but RXRs, 2 nuclear receptors that mediate biologic activities of retinoids, was significantly reduced in cells of deficient mice. This work shows that retinoids critically control the homeostasis of myeloid cell population in vivo and suggests that deficiency in this signaling pathway may contribute to various myeloproliferative disorders.
Kuwata
T
T
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, MD 20892-2753, USA.
Wang
I M
IM
Tamura
T
T
Ponnamperuma
R M
RM
Levine
R
R
Holmes
K L
KL
Morse
H C
HC
De Luca
L M
LM
Ozato
K
K
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology* / Q000503:physiopathology; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000235:genetics; D004032:Diet; D004224:Diterpenes; D005260:Female; D006098:Granulocytes / Q000473:pathology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism; D051379:Mice; D018632:Mice, Inbred SENCAR; D000084562:Retinyl Esters; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000166:cytology / Q000473:pathology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000473:pathology / Q000503:physiopathology*
D016207:Cytokines; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate