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

Abstract

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 (O2-) 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 O2-, and candidacidal activity were significantly lower in neutrophils from rats fed diets with less than or equal to 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 less than or equal to 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.