LEUKOCYTE ADHESION IN COPPER DEFICIENT MICROCIRCULATION

众所周知，有许多重要的铜依赖性酶系统密切参与免疫和炎症反应。 尽管明显的铜缺乏是罕见的，铜的需求量很小（1.5-3.0毫克/天），铜的摄入量往往接近或低于推荐的美国估计安全和充足的每日膳食摄入量，这表明边际铜缺乏可能相对常见。 霍普金斯和费拉已经证明，在通常的常规铜指标没有受到明显影响的情况下，边际铜摄入会降低中性粒细胞功能。 中性粒细胞功能中的电荷在某些人群中可能更为重要，例如铜缺乏症常见的早产儿。 然而，尽管铜的重要性和潜在的，甚至边际铜缺乏目前的健康危害，铜调节炎症反应的机制和铜缺乏水平所需的诱导这种影响是未知的。拟议的研究将集中在微循环中的损伤或感染性刺激期间膳食铜和白细胞动员之间的关系的机制。 我们以前的研究确定内皮细胞是受膳食铜缺乏影响的主要组织之一。 由于循环中的白细胞必须与内皮细胞相互作用之前，再迁移到感染或损伤部位，我们将确定如何边际和缺乏铜的摄入量影响内皮细胞与白细胞的相互作用。这些研究将证明饮食中铜摄入量的最小减少如何显著影响对炎症刺激的反应。

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.