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Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis
  1. M Hasegawa1,
  2. S Sato1,
  3. T Echigo1,
  4. Y Hamaguchi1,
  5. M Yasui2,
  6. K Takehara1
  1. 1Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
  2. 2Department of 3rd Internal Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
  1. Correspondence to:
    Assistant Professor M Hasegawa
    Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan; minoruhaderma.m.kanazawa-u.ac.jp

Abstract

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.

  • Ab, antibody
  • dSSc, diffuse cutaneous SSc
  • ELISA, enzyme linked immunosorbent assay
  • FKN, fractalkine
  • lSSc, limited cutaneous SSc
  • mTSS, modified Rodnan total skin thickness score
  • NK, natural killer
  • PBMC, peripheral blood mononuclear cells
  • SSc, systemic sclerosis
  • Tlco, carbon monoxide transfer factor
  • TNF, tumour necrosis factor
  • VC, vital capacity
  • fractalkine
  • CX3CR1
  • systemic sclerosis
  • chemokines

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