Background/Purpose: The development of giant-cell arteritis (GCA) lesions requires amplification cascades resulting in continuous recruitment of lymphocytes and monocytes. Interferon-gamma (IFNg)- induced or up-regulated chemokines CCL-2, CXCL9, CXCL10, and CXCL11 play an important role in inflammatory cell recruitment, a process in which not only endothelial cells but also vascular smooth muscle cells (VSMC) seem to be involved (Corbera-Bellalta M et al Ann Rheum Dis 2016). CX3CL1, also known as fractalkine, and along with its unique receptor CX3CR1, are the only members of CX3C chemokine/ chemokine receptor family. CX3CL1 has two isoforms mediating different functions. The transmembrane protein form regulates cell adhesion, while the soluble one (generated by proteolytic cleavage) has chemotactic function. Soluble fractalkine is elevated in serum from patients with small-vessel vasculitis. However, expression of fractalkine and its receptor have not been explored in GCA. To explore CXCL1/CXCR1 expression in GCA lesions and in temporal artery- derived VSMC. 

Methods: RNA was extracted from fresh temporal arteries of 12 GCA patients and 8 healthy controls using chloroform-isopropanol classic method. CX3CL1 mRNA expression was assessed by quantitative real-time PCR (Applied Biosystems). Fresh arteries from 1 GCA patient and 1 control were subjected to immunofluorescence using specific antibodies (Cell Signaling). VSMC obtained from cultured temporal arteries were treated with IFNg and/or TNFa for 3 days, and CX3CL1 expression by VSMC was detected by realtime PCR.

Results: CX3CL1 mRNA expression was constitutively expressed by control arteries and downregulated in GCA lesions compared with controls, probably due to VSMCs loss in the media of inflamed arteries. Consistently, immunofluorescence studies disclosed that CX3CL1 protein expression was intensively expressed by the endothelium of the GCA-involved artery and by VSMC remaining in the media. CX3CR1 was expressed by infiltrating leukocytes in GCA. As with other chemokines, CX3CL1 expression was significantly up regulated in VSMC cultured in the presence of inflammatory mediators (IFNg and TNFa). VSMC did not express CX3CR1.

Conclusion: Fractalkine and its receptor are expressed in GCA lesions. VSMCs react to the presence of inflammatory cytokines by expressing CX3CL1, highlighting a possible role of this chemokine not only in leukocyte recruitment by endothelial cells but also in leukocyte progression through the VSMC in the medial layer. Functional chemotaxis studies are ongoing to confirm this point. Supported by SAF 2014/57708-R and PIE13/00033

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fractalkine-cx3cl1-is-expressed-by-arterial-endothelium-and-vascular-smooth-muscle-cells-vsmc-in-gca/