Arrested maturation of granulocytes in copper deficient mice.
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 microg copper starting at parturition. Control mice were fed the same diet containing 6 microg 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.
Karimbakas
J
J
Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
Langkamp-Henken
B
B
Percival
S S
SS
D000818:Animals; D015415:Biomarkers; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency*; D004032:Diet; D006098:Granulocytes / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000201:enzymology; D018655:Lymphocyte Count; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000032:analysis
D015415:Biomarkers; D008070:Lipopolysaccharides; D003300:Copper; D009195:Peroxidase