Chemokines at large: in-vivo mechanisms of their transport, presentation and clearance.

Compelling evidence implicates chemokines in the induction of leukocyte emigration from blood into tissues. This arguably most fundamental effect of chemokines is accomplished by triggering cognate classical G-protein-coupled chemokine receptors on the leukocyte surface. In vitro, these same receptors mediate leukocyte migration; however, the mechanisms of chemokine-induced migration differ between in-vivo and in-vitro settings. Leukocyte egress from blood is greatly influenced by haemodynamic conditions and requires full cooperation of endothelial cells. The behaviour of chemokines in their "native habitat" in vivo is controlled by their interaction with several accessory molecules which influence immobilisation, transport, clearance and degradation of chemokines and thereby determine the sites and duration of their action. Here we discuss peculiarities of the in vivo actions of chemokines, the mechanisms of chemokine interaction with receptors and auxiliary molecules including interceptors, glycosaminoglycans and enzymes and illustrate how these interactions influence the outcome of chemokine activities in vivo.