TRACE HEAVY METAL MODIFICATION OF WOUND HEALING

拟议研究的目的是检查TRACE的效果 重金属，特别是镉和铅，对伤口愈合的影响。伤口 康复过程是一系列有组织的事件，在细胞和 分子水平涉及3个主要成分：巨噬细胞、成纤维细胞和 胶原蛋白的合成。文献表明，重金属可以 调节这些成分中的每一个的活性，尽管研究 一般不涉及伤口愈合模型。我们证明了这一点 镉暴露水平影响对皮肤同种异体移植和 并假设这是由于对伤口愈合的影响。 因此，我们建议系统地研究镉的影响和 铅对创伤相关的各种细胞和生化反应的影响 愈合，包括巨噬细胞的愈合(吞噬、胶原酶 分泌和产生调节成纤维细胞功能的因子)和 成纤维细胞(生长、增殖、胶原合成和对 巨噬细胞衍生因子)以及一些 参与胶原蛋白合成的酶。这些研究将被执行 利用损伤和正常皮肤，来自皮肤外植体的成纤维细胞， 3T3成纤维细胞系和腹膜巨噬细胞。金属暴露量 将在体内(通过饮用水)，在某些情况下，In的影响 体外暴露也将被检查。金属的影响也将是 通过细胞的组织病理学检查进行原位检查 渗透、血运重建和胶原沉积的测量 损伤和非损伤皮肤的胶原合成与血运重建 移植的皮肤。这些研究应该有助于理解 可能遇到的浓度的重金属毒性 环境，从而有助于理解重大的公共卫生 有问题。

The objective of the proposed research is to examine the effects of trace heavy metals, specifically cadmium and lead, on wound healing. The wound healing process is an organized chain of events at the cellular and molecular level involving 3 main components: macrophages, fibroblasts and collagen synthesis. The literature demonstrates that heavy metals can modulate activity in each of these components although the studies generally do not involve wound healing models. We demonstrated that low level cadmium exposure affects the response to both skin isografts and allografts and hypothesize that this is due to an effect on wound healing. Therefore, we propose to systematically examine the effect of cadmium and lead on the various cellular and biochemical responses involved in wound healing including those of macrophages (phagocytosis, collagenase secretion, and production of factors modulating fibroblast function) and fibroblasts (growth, proliferation, collagen synthesis and response to macrophage-derived factors) as well as on the activity of a number of enzymes involved in collagen synthesis. These studies will be performed utilizing wounded and normal skin, fibroblasts derived from skin explants, the 3T3 fibroblast cell line and peritoneal macrophages. Metal exposure will be in vivo (via drinking water) and in some cases, the effects of in vitro exposure will also be examined. The effects of metals will also be examined in situ through a histopathologic examination of cellular infiltration, revascularization and collagen deposition, measurement of collagen synthesis by wounded and non-wounded skin, and revascularization of grafted skin. These studies should contribute to an understanding of heavy metal toxicity at concentrations which may be encountered environmentally and thus help to understand a significant public health problem.