Arrested Maturation of Granulocytes in Copper Deficient Mice

Manuscript received 6 October 1997. Initial reviews completed 4 December 1997. Revision accepted 17 June 1998.

Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611

The objective of this study was to examine the role of copper in neutrophil development and function. Mice were made copper deficient by feeding dams a diet containing 1.05 µg copper starting at parturition. Control mice were fed the same diet containing 6 µg copper. The pups were weaned to the diet and killed when they were 5-6 wk old. Peripheral blood cell counts, margination and cell maturity were measured. The response to an intraperitoneal injection of lipopolysaccharide (LPS) was also determined. Copper deficiency resulted in twice as many neutrophils and fewer than half the number of lymphocytes. Half as many cells in copper-deficient mice expressed Ly-6G, a granulocytic marker of cell maturity. In addition, copper-deficient cells expressed only half the amount of Ly-6G per cell than was expressed by copper-adequate cells. This suggested that the cells were younger, or arrested in their maturation as a result of copper deficiency. An arrest of maturation has been proposed as the cause of neutropenia in human copper deficiency. Injection of LPS in copper-adequate mice resulted in twice as many Ly-6G-expressing cells in the periphery. LPS injection into copper-deficient mice resulted in a severe leukopenia but did not influence Ly-6G expression any more than did copper deficiency alone. LPS treatment caused an increase in myeloperoxidase activity associated with the lungs of copper-deficient mice. The results suggest that although the neutrophils of copper-deficient mice are immature, they can be sequestered by the lung when stimulated to do so.

The Journal of Nutrition Vol. 128 No. 11 November 1998, pp. 1855-1860
Copyright ©1998 by the American Society for Nutritional Sciences

This article has been cited by other articles:

				P. G. Reeves and L. C. S. DeMars Repletion of Copper-Deficient Rats with Dietary Copper Restores Duodenal Hephaestin Protein and Iron Absorption Experimental Biology and Medicine, May 1, 2005; 230(5): 320 - 325. [Abstract] [Full Text] [PDF]

				P. G. Reeves, L. C. S. DeMars, W. T. Johnson, and H. C. Lukaski Dietary Copper Deficiency Reduces Iron Absorption and Duodenal Enterocyte Hephaestin Protein in Male and Female Rats J. Nutr., January 1, 2005; 135(1): 92 - 98. [Abstract] [Full Text] [PDF]

				F. Moussaoui, I. Michelutti, Y. Le Roux, and F. Laurent Mechanisms Involved in Milk Endogenous Proteolysis Induced by a Lipopolysaccharide Experimental Mastitis J Dairy Sci, October 1, 2002; 85(10): 2562 - 2570. [Abstract] [Full Text] [PDF]

				A. B. Lentsch, A. Kato, J. T. Saari, and D. A. Schuschke Augmented metalloproteinase activity and acute lung injury in copper-deficient rats Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L387 - L393. [Abstract] [Full Text] [PDF]

				Z. L. Huang, M. L. Failla, and P. G. Reeves Differentiation of Human U937 Promonocytic Cells Is Impaired by Moderate Copper Deficiency Experimental Biology and Medicine, March 1, 2001; 226(3): 222 - 228. [Abstract] [Full Text]