Modulation of platelet and monocyte function by the chemokine fractalkine (CX3 CL1) in cardiovascular disease.

BACKGROUND

The chemokine fractalkine, CX3CL1, bears unique features within the chemokine family: it exists in a membrane bound form acting as an adhesion molecule and surface receptor; however, when cleaved by ADAM 10, it functions as a soluble chemokine. Fractalkine and its chemokine receptor CX3CR1 are known to have multiple roles in diverse human diseases, for example inflammatory diseases, rheumatoid arthritis, renal diseases and atherosclerosis.

MATERIALS AND METHODS

This review is based on the material obtained via PubMed up to November 2014. The key search terms used were 'fractalkine', 'CX3CL1', 'CX3CR1', 'cardiovascular disease', 'platelets', 'monocytes' and 'platelet-monocyte complexes'.

RESULTS

Atherosclerosis is recognized as a highly inflammatory disease, and it has become increasingly evident that the immune system plays an important role in atherogenesis and atheroprogression. Two blood cell populations are crucially involved in the early development of atherosclerotic lesions: monocytes and platelets. They are detected at vascular sites of endothelial dysfunction and are involved in inflammatory immune responses. These cells directly interact with each other, forming platelet-monocyte complexes that are increased in cardiovascular diseases. During the development of atherosclerosis, fractalkine mediates leukocyte recruitment to the inflamed endothelium, which promotes early formation of lesions. This process only effectively works in the presence of activated platelets. It has been suggested that fractalkine and its receptor contribute to platelet-monocyte aggregate formation underlining the two important impacts of this chemokine for platelets as well as monocytes.

CONCLUSION

Interesting data hint at a role of fractalkine for platelet activation, adhesion and subsequent monocyte recruitment to activated endothelial cells in cardiovascular diseases. However, the exact mechanisms remain to become unravelled.