Abstract 3709: Fractalkine Modulates Recruitment Of Monocytic Cells Following Rupture Of Atherosclerotic Plaque
Objective: The membrane-bound chemokine fractalkine (CX3CL1) is expressed in the atherosclerotic vascular wall. Mice deficient in the fractalkine receptor (CX3CR1) are protected from atherosclerotic lesion development. The aim of our study was to dissect the role of fractalkine expressed in plaque for the recruitment of monocytic cells in vivo.
Methods and Results: Using immunohistological analysis we show that human and murine atherosclerotic carotid arteries express CX3CL1 on endothelium, macrophages and smooth muscle cells. Using intravital videofluorescence microscopy we then studied monocyte recruitment to the atherosclerotic carotid artery of 18-wk-old ApoE−/− mice. We found that adhesion of DCF-labeled monocytic cells to atherosclerotic endothelium is strongly inhibited by pre-injection of a neutralizing CX3CL1-antibody as compared to control IgG. In the same model, we then quantified leukocyte recruitment following ligature-induced rupture of atherosclerotic plaque. We determined an increased number of adherent monocytic cells to the injured vascular wall. However, the presence of a CX3CL1-antibody again markedly reduced recruitment of monocytic cells. Further, adhesion at the site of vascular injury was only minimal when CX3CR1 surface expression on monocytic cells is silenced by siRNA-technique, indicating that their recruitment is modulated by the CX3CR1-CX3CL1 axis.
Conclusion: CX3CL1 expressed in the atherosclerotic vascular wall modulates the recruitment of monocytic cells, an essential step in the development and progression of atherosclerotic lesions. Occurrence of plaque rupture enhances CX3CR1-CX3CL1-dependent monocyte adhesion.