Title

Manipulation and detection of metallothionein with an anti-metallothionein monoclonal antibody

Date of Completion

January 2005

Keywords

Biology, Cell

Degree

Ph.D.

Abstract

Exposure to environmental toxicants can result in a variety of changes in immune function. One of the ways that cells counter toxicant effects is to increase the expression of stress response proteins. Metallothionein (MT) is a small stress protein that can be induced by exposure to heavy metal cations, oxidative stressors, and acute phase cytokines that mediate inflammation, and can contribute to changes in immune function. ^ The present study was designed to explore the role of endogenous MT in humoral immunity. The endogenous MT synthesized during the normal immune responses, toxicant exposure or inflammation can result in the release of MT to the extracellular environment. This extracellular MT has immunosuppressive effects on the humoral immune response. An anti-metallothionein monoclonal antibody (clone UC1MT) can enhance the humoral immune response by blocking the suppressive effects of MT. ^ We have also determined the presence of intracellular MT in different conditions, and examined the interaction of MT with leukocyte plasma membranes using UC1MT monoclonal antibody. The evidence demonstrates that MT released as a consequence of immune activation, toxicant exposure or inflammation interacts with the plasma membranes. The interaction of MT with elements of the immune system can result in an altered immune response by affecting the ability of the immune effector cells to function under certain circumstances. ^ Taken together, these observations suggest that MT has a critical role to play in the development of a normal immune response. The agents that elicit MT synthesis may alter immune function via an MT-mediated mechanism. The manipulation of MT levels with an anti-MT monoclonal antibody may have important therapeutic implications in the treatment of immune dysfunctions. The extracellular MT interactions with immune effector cells may prove to be a useful therapeutic target for the manipulation of undesirable immune effects caused by toxicants and other stressful agents. ^