%0 Journal Article
%T Metallothionein mediates leukocyte chemotaxis
%A Xiuyun Yin
%A David A Knecht
%A Michael A Lynes
%J BMC Immunology
%D 2005
%I BioMed Central
%R 10.1186/1471-2172-6-21
%X In the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis.These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure.Initiation of an immune response is accompanied by physiological changes that can produce a stressful environment for both the cells involved in the immune response, and for bystander cells that are part of adjacent but uninvolved tissues. These stresses can be further increased by the presence of infectious microorganisms. The changes to the environment include increases in reactive oxygen and reactive nitrogen species, products of cellular metabolism, and agents that initiate apoptotic or necrotic cell death.Cells react to stressful environments with a broad range of different homeostatic responses. These responses can include the synthesis of a host of stress response proteins, including the heat shock proteins, acute phase cytokines, and metallothionein. Metallothionein is a novel member of thi
%U http://www.biomedcentral.com/1471-2172/6/21