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Ann Rheum Dis. Jan 2005; 64(1): 21–28.
PMCID: PMC1755178

Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis


Background: Fractalkine expressed on endothelial cells mediates activation and adhesion of leucocytes expressing its receptor, CX3CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX3CR1.

Objective: To determine the role of fractalkine and its receptor in systemic sclerosis (SSc) by assessing their expression levels in patients with this disease.

Methods: The expression of fractalkine and CX3CR1 in the skin and lung tissues was immunohistochemically examined. Circulating soluble fractalkine levels were examined by enzyme linked immunosorbent assay (ELISA). Blood samples from patients with SSc were stained for CX3CR1 with flow cytometric analysis.

Results: CX3CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX3CR1, including monocytes/macrophages, were increased in the lesional skin and lung tissues from patients with diffuse cutaneous SSc. Fractalkine was strongly expressed on endothelial cells in the affected skin and lung tissues. Soluble fractalkine levels were significantly raised in sera and were associated with raised erythrocyte sedimentation rates, digital ischaemia, and severity of pulmonary fibrosis.

Conclusions: Up regulated expression of fractalkine and CX3CR1 cooperatively augments the recruitment of mononuclear cells expressing CX3CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.

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Selected References

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Figures and Tables

Figure 1
 (A) CX3CR1 expression in normal skin tissues (CTL) and lesional skin tissues from patients with dSSc with rapidly progressing skin thickening. (B) CX3CR1 expression in normal lung tissues and affected lung tissues from patients with dSSc with ...
Figure 2
 Representative expression of CX3CR1 on PBMC from patients with dSSc and normal controls. All samples were stained in parallel by two colour immunofluorescence staining and analysed sequentially by flow cytometry with identical instrument setting. ...
Figure 3
 Expression of CX3CR1 on leucocyte subpopulations from patients with lSSc, patients with dSSc, and normal controls. CX3CR1 levels were assessed by two colour immunofluorescence staining with flow cytometric analysis. All samples were stained ...
Figure 4
 (A) FKN expression in normal skin tissues and skin tissues from patients with dSSc with rapidly progressing skin thickening. (B) FKN expression in normal lung tissues and affected lung tissues from patients with dSSc with progressive pulmonary ...
Figure 5
 (A) Serum levels of sFKN in patients with patients with lSSc, patients with dSSc, and normal controls (CTL). (B) Serum levels of sFKN in patients with SSc with (PF+) and without (PF–) pulmonary fibrosis. Soluble FKN levels were determined ...
Figure 6
 Correlations of serum sFKN levels with laboratory data in patients with SSc. The correlation of sFKN levels with (A) %VC and (B) TLCO is shown. Soluble FKN levels were determined using a specific ELISA.

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