Chemokine patterning by glycosaminoglycans and interceptors

Abstract

Chemokines mediate leukocyte emigration from blood into tissues. This process is triggered by chemokines binding and signaling through their cognate G-protein-coupled receptors on leukocytes and requires the involvement of leukocyte and endothelial cell adhesion molecules. Additionally, in vivo chemokine activity depends on their interaction with "auxiliary" molecules expressed by the vascular endothelial cells. Secreted chemokines can be immobilized on the luminal and abluminal endothelial cell surfaces by glycosaminoglycans. In order to be targeted to their presentation sites on the luminal endothelial cell surface, the tissue-derived chemokines have to cross the endothelial cell barrier. For inflammatory chemokines this is accomplished by active transport involving Duffy antigen, an 'interceptor' expressed by venular endothelial cells. Other chemokine interceptors, D6 in particular, may act as scavenging decoys and are involved in clearance of chemokines. The interceptor-mediated transport or elimination of chemokines, together with their immobilization by glycosaminoglycans, lead to chemokine patterning at the blood-tissue interface and within tissues. The resulting chemokine gradients induce leukocyte emigration from blood and may also be necessary for directed leukocyte migration within tissues.