Moderate zinc deficiency in rhesus monkeys. An intrinsic defect of neutrophil chemotaxis corrected by zinc repletion.

Experimental animals fed zinc-deficient diets are well known for susceptibility to infections and impaired mitogen response and Ig production. However, the levels of zinc deficiency used have generally been severe, not comparable to human populations, and have not addressed neutrophil function. To address this issue we have studied the effect in rhesus monkeys of a well defined moderately zinc-deficient (MZ) diet on polymorphonuclear leukocyte (PMN) function. Female adult rhesus monkeys were fed either a control (100 micrograms Zn/g) or MZ (2 micrograms Zn/g) diet for 9 mo with quantitation of PMN chemotaxis, and phagocytosis of opsonized yeast. In addition, membrane potential and secretion responses (changes in 90 degrees light scatter) and changes in PMN shape (forward light scatter shifts) were also measured. When compared to the PMN of animals fed control diets, there was a significant reduction in chemotaxis to FMLP of MZ-fed monkey PMN. Although shape change, cell membrane depolarization, as well as phagocytosis were not significantly different among the two groups, the PMN of MZ animals had significantly lower relative loss of orthogonal light scatter (degranulation) due primarily to a lower resting orthogonal light scatter and also a smaller loss when stimulated with FMLP. In vitro addition of zinc to the cells (25 microM) did not improve chemotaxis, and in fact, was inhibitory for most control and zinc-deficient cells. However, after 2 wk of dietary zinc repletion (100 micrograms Zn/g), chemotaxis in the low zinc group was higher and comparable to the control response. These data indicate that zinc deficiency is associated with an intrinsic PMN defect that specifically affects chemotaxis and is corrected with dietary zinc repletion.