LEUKOCYTE ADHESION IN COPPER DEFICIENT MICROCIRCULATION

众所周知，有许多重要的铜依赖酶系统与免疫和炎症反应密切相关。尽管明显的铜缺乏很少见，铜的需求量很小(1.5-3.0毫克/天)，但铜的摄入量往往接近或低于美国估计的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。霍普金斯和法拉已经证明，在铜的常规指标没有受到明显影响的情况下，边际铜摄入量会降低中性粒细胞的功能。在一些人群中，中性粒细胞功能的电荷可能会产生更大的影响，例如早产儿，那里的铜缺乏很常见。然而，尽管铜很重要，即使是轻微的铜缺乏也有可能对健康构成危害，但铜调节炎症反应的机制以及引发这种影响所需的铜缺乏程度尚不清楚。这项拟议的研究将侧重于膳食铜与微循环中损伤或感染性刺激期间白细胞动员之间的关系的潜在机制。我们先前的研究发现，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在转移到感染或损伤部位之前必须与内皮细胞相互作用，我们将确定边缘和不足的铜摄入量如何影响内皮细胞与白细胞的相互作用。这些研究将证明，饮食中铜摄入量的微小下降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.