Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus and activation-regulated chemokine, are expressed in human atherosclerotic lesions

Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atheroscl erotic lesions may play an important role in mononuclear cell recruitment a nd macrophage differentiation. We have analyzed the expression of the linke d chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL2 2), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX3C c hemokine fractalkine (CX(3)CL1) in primary macrophages and human atheroscle rotic lesions by reverse transcription-polymerase chain reaction and immuno histochemistry. We show that macrophage expression of the chemokines MDC, f ractalkine, and TARC is upregulated by treatment with the Th2-type cytokine s interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalki ne mRNA expression are seen in some. but not all, human arteries with advan ced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalki ne, and TARC are expressed by a subset of macrophages within regions of pla ques that contain plaque microvessels, We conclude that MDC, fractalkine, a nd TARC, which are chromosome 16q13 chemokines, could play a role in mononu clear cell recruitment into atherosclerotic lesions and influence the subse quent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.