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Retinol Is Sequestered in the Bone Marrow of Vitamin A-Deficient Rats^1,2,

Sally S. Twining^*,,3, David P. Schulte^*, Patricia M. Wilson^*, Brian L. Fish and John E. Moulder

^* Department of Biochemistry Department of Ophthalmology Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226

Retinoic acid bound to the nuclear retinoic acid receptor- is required for the differentiation of promyelocytes to mature neutrophils. However, severely vitamin A-deficient rats have normal numbers of neutrophils in the blood and inflamed tissues. This paradox was explored using four dietary groups of rats: 1) vitamin A-deficient rats; 2) vitamin A-deficient rats subsequently receiving vitamin A; 3) weight-matched pair-fed rats; and 4) nonrestricted, vitamin A-complete diet-fed rats. Plasma and liver retinol concentrations of the vitamin A-deficient rats were <1% of those of the other three groups. In contrast, the bone marrow retinol concentrations of the vitamin A-deficient rats were fourfold higher than those in the other three groups. The distribution of myeloid-derived cells in the bone marrow was similar in all four groups of rats with the exception of a significantly greater (P < 0.05) occurrence of hypersegmented neutrophils (six or more lobes) in the vitamin A-deficient rats (2.1%) relative to the control groups (0–0.1%). The blood of the vitamin A-deficient rats also contained significantly higher numbers (P < 0.01) of hypersegmented neutrophils (67%) relative to those in the control groups (2–7%). The hypersegmentation of the neutrophils in this group of rats was not due to a concurrent deficiency of vitamin B-12 or folate. The importance of bone marrow-derived cells to the survival of the animal is suggested by retinol sequestration in the bone marrow of vitamin A-deficient rats, allowing the differentiation of myeloid cells to neutrophils.

KEY WORDS: • vitamin A deficiency • bone marrow • neutrophil hypersegmentation • rats

¹ Supported in part by grants RO1EY-08388 and P3OEY-01931 from the National Eye Institute-National Institute of Health and a grant from the Thrasher Research Fund.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 2 October 1995. Revision accepted 6 February 1996.

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