Platelets, endothelial cells, inflammatory chemokines, and restenosis: complex signaling in the vascular play book.

Adhesive and signaling interactions between endothelial cells and leukocytes are key mechanisms that mediate both targeting of the blood cells to specific sites and information transfer that results in change in their phenotypes and function.1 These events are beneficial in defense against microbes and wound surveillance and repair; however, in dysregulated inflammatory conditions such as atherosclerosis and its complications, including acute coronary syndromes and restenosis after interventional procedures, accumulation and activation of leukocytes can injure the host. The cell–cell interactions and signaling mechanisms are complex in the game of inflammation, and there are a number of players. In addition to endothelial cells and leukocytes, platelets contribute to leukocyte accumulation and to changes in their behavior in both physiological and pathological conditions,2,3,4⇓⇓ emphasizing the intimate relationship between the thrombotic and inflammatory systems. See p 1523 One mechanism involves direct adhesion of activated platelets to monocytes, neutrophils, or other leukocyte subclasses and binding of chemokines or lipid signaling molecules that are released from the platelets or displayed in a juxtacrine fashion on their surfaces (see below), to receptors on the leukocyte plasma membrane.3,5⇓ In this issue of Circulation , Schober and co-workers6 report a different play in the inflammatory repertoire: platelets interacting with inflamed endothelial cells donate the CC chemokine regulated upon activation normal T cell expressed presumed secreted (RANTES) to the endothelial surface, where it acts as a cell-associated signal for adhesion of monocytes. A number of the observations were made with cultured endothelial monolayers, incubated under conditions of stasis or flow, and isolated leukocytes; a caveat is that these experiments were done with proprietary endothelial cells and a monocytic cell line rather than primary leukocytes. In addition, however, other strategies added to the findings. Receptor blocking experiments indicated that RANTES signaling contributes to …