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Copper Status and Function of Neutrophils Are Reversibly Depressed in Marginally and Severely Copper-Deficient Rats^,21,

Vitamin and Mineral Nutrition Laboratory, Beltsville, Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705 and Nutritional Sciences Program, University of Maryland, College Park, MD 20742

Weaned male rats were pair-fed diets containing either adequate (7 mg/kg diet; +Cu) or deficient (0.7 mg/kg diet; -Cu) levels of copper for 5 wk. Cellular Cu concentration, activity of Cu,Zn superoxide dismutase (Cu,Zn-SOD), generation of superoxide anion (O) in response to opsonized zymosan and phorbol myristate acetate, and candidacidal activity in elicited neutrophils were all significantly decreased by dietary Cu deficiency. Furthermore, survivability of Candida albicans injected into the peritoneal cavity of Cu-deficient rats was greater than in controls. Phagocytic activity of neutrophils was independent of cellular Cu status. To determine whether the impaired function of neutrophils was also characteristic of marginal Cu deficiency, weaned rats were fed diets containing either 0.6, 1.1, 2.0, 2.7 or 6.7 (control) mg Cu/kg for 5 wk. The activity of Cu,Zn-SOD, phorbol myristate acetate-induced production of O, and candidacidal activity were significantly lower in neutrophils from rats fed diets with 2.7 mg Cu/kg compared to control cells. In contrast, decreased tissue Cu and the activity of erythrocyte Cu,Zn-SOD were observed only when dietary Cu was 2.0 mg/kg. Reduced SOD activity, respiratory burst and candidacidal activity of neutrophils were evident as soon as 1 wk after initiating the dietary treatment. Feeding +Cu diet to Cu-deficient rats for 1 wk restored Cu status and function of neutrophils to control levels. These results show that neutrophil function is reversibly impaired by marginal and severe Cu deficiency and suggest that the Cu status and function of these cells may provide a sensitive indicator for assessment of Cu status.

KEY WORDS: • copper • neutrophils • respiratory burst • microbicidal activity • rats

¹ This work was presented in part at the 74th Annual Meeting of the Federation of American Societies for Experimental Biology, Washington, D.C., April 1990 [BABU, U. & FAILLA, M. L. (1990) Respiratory burst and candidacidal activity are impaired in peritoneal macrophages and neutrophils from marginally and severly copper deficient rats. FASEB J. 4: A509 (abs. 1409)].

² Address correspondence to: Dr. Mark L. Failla, USDA, ARS, BHNRC, VMNL, Bldg. 307, Rm. 205, BARC-East, Beltsville, MD 20705.

Manuscript received 4 April 1990. Revision accepted 6 June 1990.

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