Characterisation of fractalkine/CX3CL1 and fractalkine receptor (CX3CR1) expression in abdominal aortic aneurysm disease.
OBJECTIVE
Fractalkine (CX3CL1) promotes adhesion and extravasation of leucocytes through interactions with fractalkine receptor (CX3CR1) expressed on CD56+/CD16+ NK cells and CD8+ T cells. The current study aims to test the hypothesis the CX3CL1-CX3CR1 interaction contributes to the inflammatory infiltrate in AAA tissue.


METHODS
Immunohistochemistry (IHC) was used to define expression of CX3CR1 in AAA tissue. Multi-parametric flow cytometry (FC) was used to determine CX3CR1 expression on T-cells (CD3+) and NK cells (CD56+) from AAA tissue and peripheral blood of AAA patients and healthy controls. Regulation of CX3CL1 expression by vascular endothelial (vEC) and smooth muscle cells (vSMC) was examined in vitro using primary cell cultures.


RESULTS
CX3CR1+ cells were detected in 19/28 AAA tissue samples and predominately localised in the adventitia. PBMCs from patients with AAA demonstrated higher percentages of CX3CR1+ NK cells (60.0-88.6%) and T cells (7.5-39.4%) compared with healthy controls. Furthermore, the frequency of CX3CR1+ NK cells (91%) and T cells (94%) in inflammatory AAA tissue were higher than in atherosclerotic AAA tissue. The pro-inflammatory cytokine TNFalpha increased expression of fractalkine by vSMC and vEC.


CONCLUSIONS
CX3CL1+ and CX3CR1+ cells are present in AAA disease and their interaction may contribute to the recruitment of inflammatory cells seen in AAA tissue.
Patel
A
A
Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK.
Jagadesham
V P
VP
Porter
K E
KE
Scott
D J A
DJ
Carding
S R
SR
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology* / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha