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Fast track to vascular disease
Date:6/3/2011

blood vessel, and can induce and chronically perpetuate an inflammatory response. Cells of the immune system migrate to the site of the primary lesion and release signaling molecules that attract other types of immune cells which facilitate plaque formation. The atherosclerotic plaques in turn serve as sources of additional signals and mediators, the inflammation reaction gets out of control and continues unchecked, and plaque growth progressively obstructs the flow of blood.

So-called dendritic cells are responsible for determining the targets against which the immune response is directed. They do so by using fragments of target-specific proteins displayed in a molecular complex on their surfaces to activate immune cells called T cells. The T cells have highly variable receptors that enable them to recognize such complexes and to identify the intact target. "Dendritic cells are detectable in arteries and in atherosclerotic tissue, but their precise function in the pathogenesis of plaques has been unclear," explains Weber. "We were particularly interested in learning more about the role of the chemokine CCL17 - a signal protein that is specifically synthesized by mature dendritic cells - in the activation of T cells and in regulating T cell homeostasis."

For their experiments the researchers made use of a transgenic mouse strain in which the gene for CCL17 had been replaced by a DNA sequence encoding the genetic information for the Green Fluorescent Protein (GFP). Thus, in this strain, GFP acts as a proxy for CCL17-producing cells. Since GFP can be visualized by virtue of its fluorescence, the team was able to determine where CCL17-producing cells would normally congregate. This approach also allowed them not only to work out the effects of the lack of CCL17, but also to use advanced methods of microscopy, in particular multiphoton microscopy, to follow how the dendritic cells intrude and accumulate in atherosclerotic plaques and interact with T
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Contact: Dr. Christian Weber
kreislaufinstitut@med.uni-muenchen.de
49-895-160-4350
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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