Smooth muscle cells in human atherosclerotic plaques express the fractalkine receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine fractalkine (CX3CL1).
BACKGROUND
Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX3CL1) is an unusual membrane-bound chemokine that mediates chemotaxis through the CX3CR1 receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been described that are associated with coronary artery disease.


RESULTS
We investigated the expression of the CX3C chemokine fractalkine and its receptor CX3CR1 in human coronary artery plaques by immunocytometry. We show that a subset of mononuclear cells expresses high levels of fractalkine in human coronary atherosclerotic plaques and that smooth muscle cells within the neointima express the fractalkine receptor CX3CR1. There is a positive correlation between the number of fractalkine-expressing cells and the number of CX3CR1-positive cells in human atherosclerotic plaques (r=0.70, n=15 plaques). Furthermore, we demonstrate that cultured vascular smooth muscle cells express the CX3CR1 receptor and undergo chemotaxis to fractalkine that can be inhibited by G protein inactivation by pertussis toxin.


CONCLUSIONS
These results suggest that in human atherosclerosis, fractalkine, rather than mediating inflammatory cell recruitment, can act as a mediator of smooth muscle cell migration.
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Andrew D
AD
Lucas
Christina
C
Bursill
Tomasz J
TJ
Guzik
Jerzy
J
Sadowski
Keith M
KM
Channon
David R
DR
Greaves
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D017252:CD3 Complex / Q000096:biosynthesis; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism* / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D037342:Pertussis Toxin / Q000494:pharmacology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D037342:Pertussis Toxin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C515538:CX3CL1 protein, human