Characterization of fractalkine (CX3CL1) and CX3CR1 in human coronary arteries with native atherosclerosis, diabetes mellitus, and transplant vascular disease.
BACKGROUND
Fractalkine is a novel chemokine that mediates both firm adhesion of leukocytes to the endothelium via CX3CR1 and leukocyte transmigration out of the bloodstream. Fractalkine has recently been shown to play a role in the pathogenesis of acute organ rejection. Since its expression is regulated by inflammatory agents such as LPS, IL-1, and TNF-alpha, fractalkine involvement in atherosclerosis and transplant vascular disease (TVD) is of particular interest. In this study, we characterized the presence of fractalkine and its receptor CX3CR1 in human coronary arteries from normal, atherosclerotic, diabetic, and TVD settings.


METHOD
Polyclonal rabbit antibodies were used to immunostain human fractalkine and CX3CR1 to localize their presence in transverse sections of the proximal left anterior descending and/or right coronary arteries. Slides were scored in a blinded fashion for intensity of staining (0 to 4+) and for localization in vessel walls.


RESULTS
Normal coronary arteries showed no fractalkine staining. In atherosclerotic coronary arteries, staining was localized to the intima, media, and adventitia. Within the media, fractalkine expression was seen in macrophages, foam cells, and smooth muscle cells (SMCs). Diabetic vessels showed similar staining patterns to atherosclerotic coronaries, with much stronger staining in the deep intima. Transplanted coronaries showed staining in the endothelium, intima, and adventitia in early disease, and intimal, medial, and adventitial staining in late disease. CX3CR1 staining was seen in the coronary arteries of all cases, with specific localization to regions with fractalkine staining.


CONCLUSION
The distinctive staining patterns in native atherosclerosis, diabetes mellitus with atherosclerosis, and TVD indicate that the expression of fractalkine and CX3CR1 may be important in the pathogenesis of these diseases.