BACKGROUND: Metallothionein (MT) is a @entity462 -rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines @entity14420 and @entity17184 . @entity462 motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor. RESULTS: 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 @entity1919 signaling pathway to initiate @entity6722 . CONCLUSION: These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of @entity32 . 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 @entity102 , may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with @entity792 and toxicant exposure.

Metallothionein mediates leukocyte XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity6722 :: ('MESH:C565534', 'Disease') :: ['chemotaxis'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine', 'Cysteine'] @entity102 :: ('MESH:D002908', 'Disease') :: ['chronic inflammatory disease'] @entity14420 :: ('6361', 'Gene') :: ['Ccl17'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['cyclic AMP'] @entity17184 :: ('6376', 'Gene') :: ['Cx3cl1'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disease']
@entity6722 :: (MESH:C565534,Disease) :: ['chemotaxis']
