Chemokine-mediated recruitment of inflammatory and smooth muscle cells in transplant-associated arteriosclerosis

Despite continued improvement in therapies to prevent acute allograft rejection, transplant-associated arteriosclerosis remains a major long-term limitation to successful solid organ transplantation. Ongoing intimal hyperplasia of arterioles results in progressive vascular stenosis with consequent graft ischemia. The process is driven by successive waves of inflammatory cell infiltrates beginning with cells of acute and chronic innate immunity and culminating in alloantigen-specific T cells. Finally, smooth muscle cells, largely derived from host precursor cells, are also recruited into the vessel intima where they proliferate and produce extracellular matrix. The process of inflammatory cell and smooth muscle cell recruitment depends on the coordinated production of chemokines, produced both by graft endothelial cells as well as by previously recruited host inflammatory cells. This article reviews recent progress in our understanding of these small molecular weight mediators and suggests potential novel therapeutic intervention via blockade of chemokine and chemokine receptor interactions.