EFFECTS OF TOXIC METALS ON IMMUNITY

有毒金属对免疫力的影响

基本信息

批准号：
3250130
负责人：
RICHARD A WINCHURCH
金额：
$ 6.95万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-03-01 至 1987-02-28
项目状态：
已结题

项目摘要

Cadmium and lead are agents which produce a variety of adverse physiological effects including alterations of immune functions. However, the full spectrum of their activity has not yet been defined and the mechanisms which they produce their effects are unknown. It is known that the distribution and retention of these metals differs in newborns and adults, but the consequences of these differences on the development of the immune system during the perinatal period are unknown. In this application we propose to compare the effects of lead and cadmium on both cellular and humoral immune responses in adult and neonatal mice. We will determine critical dose-response relationship by measuring discrete immune functions, i.e., cellular and humoral responses, and by measuring metal content in various lymphoid and non-lymphoid tissue. Within these studies, we will examine metal distribution in functionally distinct subpopulations of lymphocytes. In each of these systems we will study possible interactions between cadmium or lead on zinc metabolism in order to determine if the toxic effects of these metals are related to a disruption of essential trace metal metabolism. Since the protein, metallothionein, is centrally involved in the metabolism of both zinc and cadmium, we will measure metallothionein levels in various tissues and cell types. Finally, because bacterial endotoxins are known to produce a variety of effects on immune function and since some effects of endotoxin are potentiated by both cadmium and lead, we will study possible roles of endotoxin on immunomodulation in metal treated mice.

镉和铅是产生多种不良的代理生理影响，包括免疫功能的改变。然而，他们的全部活动尚未定义产生其影响的机制未知。众所周知这些金属的分布和保留在新生儿和成年人，但是这些差异对发展的后果围产期期间的免疫系统尚不清楚。在此应用程序中我们建议比较铅和镉对细胞和细胞的影响成年和新生小鼠的体液免疫反应。我们将确定通过测量离散免疫功能，关键的剂量反应关系，即细胞和体液反应，以及通过测量金属含量各种淋巴机和非淋巴组织。在这些研究中，我们将检查金属在功能上不同的亚群中的金属分布淋巴细胞。在每个系统中，我们将研究可能的相互作用在镉代谢上的镉或铅之间，以确定是否是这些金属的毒性作用与必不可少的破坏有关痕量金属代谢。由于蛋白质，金属硫硫蛋白是集中的参与锌和镉的代谢，我们将测量各种组织和细胞类型中的金属硫蛋白水平。最后，因为已知细菌内毒素会对免疫产生多种影响功能和由于内毒素的某些作用都被两者增强镉和铅，我们将研究内毒素在金属处理小鼠的免疫调节。