TRACE HEAVY METAL MODIFICATION OF WOUND HEALING

微量重金属对伤口愈合的影响

• 批准号: 3250503
• 负责人: IRVING GRAY
• 金额: $ 14.32万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-28 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250503
• 关键词: atomic absorption spectrometry; cadmium; collagenase; environmental toxicology; fibroblasts; histopathology; ions; lead; lead poisoning; macrophage; metal poisoning; phagocytosis; radiotracer; skin; skin transplantation; tissue /cell culture; trace elements; wound healing

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.

拟议研究的目的是检查痕迹的影响 重金属，特别是镉和铅，对伤口愈合有影响。 伤口 愈合过程是细胞和细胞中一系列有组织的事件链 分子水平涉及3个主要成分：巨噬细胞、成纤维细胞和 胶原蛋白合成。 文献表明，重金属可以 调节这些成分的活性，尽管研究 一般不涉及伤口愈合模型。 我们证明了低 镉暴露水平会影响同种皮肤移植物的反应 同种异体移植物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和 导致伤口中涉及的各种细胞和生化反应 愈合，包括巨噬细胞的愈合（吞噬作用、胶原酶 调节成纤维细胞功能的因子的分泌和产生）和 成纤维细胞（生长、增殖、胶原蛋白合成和对 巨噬细胞衍生因子）以及许多活性 参与胶原蛋白合成的酶。 这些研究将进行 利用受伤和正常的皮肤，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 将在体内（通过饮用水），并且在某些情况下，体内的影响 还将检查体外暴露。 金属的影响也会 通过细胞组织病理学检查进行原位检查 浸润、血运重建和胶原沉积、测量 受伤和非受伤皮肤的胶原蛋白合成以及血运重建 的移植皮肤。 这些研究应该有助于理解 可能遇到的浓度下的重金属毒性 环境，从而有助于了解重要的公共卫生 问题。