It is well established that there are a number of important copper-dependent enzyme systems that are intimately involved in immunologic and inflammatory responses. Even though overt copper deficiency is rare and the copper requirement is small (1.5-3.0 mg/day), the intake of copper is often near or below the recommended U.S. Estimated Safe and Adequate Daily Dietary Intakes suggesting that marginal copper deficiency may be relatively common. Hopkins and Failla have shown that marginal copper intake reduces neutrophil function under conditions where the usual conventional indicators of copper are not markedly affected. Charges in neutrophil function may be even more consequential in some populations such as premature infants where copper deficiency is common. Yet, despite the importance of copper and the potential of even marginal copper deficiency to present a health hazard, the mechanisms by which copper modulates inflammatory reactions and the level of copper deficiency necessary to induce such effects are not known. The proposed research will focus on mechanisms underlying the relationship between dietary copper and the mobilization of leukocytes during injury or infectious stimuli in the microcirculation. Our previous research identified the endothelium as one of the major tissues affected by dietary copper deficiency. Since circulating leukocytes must interact with the endothelium prior to transmigration to sites of infection or injury, we will determine how marginal and deficient copper intake affect endothelial interactions with leukocytes. The studies will demonstrate how minimal decreases in dietary copper intake can significantly influence the response to inflammatory stimuli.