The role of CX3CL1 and ADAM17 in pathogenesis of diffuse parenchymal lung diseases

Abstract

Background: Fractalkine (CX3CL1) is unique chemokine that functions as chemoattractant on the fractalkine receptor (CX3CR1) expressing effector cytotoxic lymphocytes and macrophages. CX3CL1 exists in two forms – soluble and membrane-bound form. Soluble CX3CL1 is released from cell membranes by proteolysis by TNF-α-converting enzyme/disintegrin-like metalloproteinase 17 (TACE/ADAM17) and ADAM10. In this study, we evaluated the role of CX3CL1 and ADAM17 in pathogenesis of diffuse parenchymal lung diseases (DPLDs).

Methods: The concentration of CX3CL1 and ADAM17 was measured by the enzyme-linked immunosorbent assay test in bronchoalveolar lavage fluid of patients affected by sarcoidosis, idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and connective tissue disease–associated interstitial lung disease.

Results: Patients with IPF and HP had significantly higher CX3CL1 concentration (p<0.05) compared to control group (CG). Significantly higher concentration of CX3CL1 was measured in fibrotic DPLDs compared to non-fibrotic DLPDs (p<0.0001). We found a positive correlation of CX3CL1 concentration with CD8+T cells and negative correlation with CD4+T cells and diffusion capacity for carbon monoxide (DLCO). Concentration of ADAM17 was significantly lower in IPF group compared to other DPLD groups. We noticed significantly higher values of CX3CL1/ADAM17 ratio in the IPF group compared to other DPLD groups.

Measurements and Main Results: CX3CL1 acts in the pathogenesis of DPLDs and the concentration strongly correlates with the severity of lung parenchyma impairment evaluated by measurement of DLCO. We demonstrated the relationship of the high concentration of CX3CL1 to low concentration of ADAM17 in IPF.