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, CX(3)CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX(3)CR1.


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 CX(3)CR1 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 CX(3)CR1 with flow cytometric analysis.


RESULTS
CX(3)CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX(3)CR1, 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 CX(3)CR1 cooperatively augments the recruitment of mononuclear cells expressing CX(3)CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.
Hasegawa
M
M
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan. minoruha@derma.m.kanazawa-u.ac.jp
Sato
S
S
Echigo
T
T
Hamaguchi
Y
Y
Yasui
M
M
Takehara
K
K
D000328:Adult; D000368:Aged; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000097:blood / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism; D018121:Receptors, Cytokine / Q000097:blood / Q000378:metabolism*; D015728:Receptors, HIV / Q000097:blood / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism; D015854:Up-Regulation
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV