Abstract
Fractalkine (CX3CL1) is a unique chemokine that functions as a chemoattractant for effector cytotoxic lymphocytes and macrophages expressing fractalkine receptor CX3CR1. CX3CL1 exists in two forms—a soluble and a membrane-bound form. The soluble CX3CL1 is released from cell membranes by proteolysis by the TNF-α-converting enzyme/disintegrin-like metalloproteinase 17 (TACE/ADAM17) and ADAM10. In this study, we evaluated the diagnostic relevance and potential roles of CX3CL1 and ADAM17 in the pathogenesis of diffuse parenchymal lung diseases (DPLDs) in the human population. The concentration of CX3CL1 and ADAM17 was measured by the enzyme-linked immunosorbent assay (ELISA) test in bronchoalveolar lavage fluids of patients suffering from different DPLDs. The concentration of CX3CL1 was significantly higher in patients suffering from idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis patients compared to the control group. A significantly higher concentration of CX3CL1 was measured in fibrotic DPLDs compared to non-fibrotic DLPD patients. We found a positive correlation of CX3CL1 levels with the number of CD8+ T cells, and a negative correlation with CD4+ T cells in BALF and diffusion capacity for carbon monoxide. The concentration of ADAM17 was significantly lower in the IPF group compared to the other DPLD groups. We noticed a significantly higher CX3CL1/ADAM17 ratio in the IPF group compared to the other DPLD groups. We suggest that CX3CL1 has a distinctive role in the pathogenesis of DPLDs. The level of CX3CL1 strongly correlates with the severity of lung parenchyma impairment. The results suggest that high values of CX3CL1/ADAM17 could be diagnostic markers for IPF.
Highlights
Diffuse parenchymal lung diseases (DPLDs) comprise a broad heterogeneous group of diseases with more than 200 various diagnostic units
The aim of this study was to determine the level of CX3CL1 in the bronchoalveolar lavage fluid (BALF) of patients affected by particular diffuse parenchymal lung diseases (DPLDs)—pulmonary sarcoidosis (PS), idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and connective tissue disease-associated interstitial lung disease (CTDILD)
In comparison among different DPLD groups, we found significantly lower CX3CL1 concentrations in the PS group (p < 0.001) compared to all other DPLD groups (IPF, HP, connective tissue disease-associated interstitial lung disease (CTD-ILD))
Summary
Diffuse parenchymal lung diseases (DPLDs) comprise a broad heterogeneous group of diseases with more than 200 various diagnostic units. The common feature of DPLDs is the involvement of the lung interstitium characterized by different degrees of inflammation and fibrosis with extracellular matrix accumulation [1]. The prognosis depends on the underlying immunopathological process, which is in the vast majority of cases an inflammatory response to a known or unknown trigger. The continuing inflammatory process can result in the activation of the fibrosing processes [2]. The worst prognosis is related to the progressive fibrotic phenotype of the disease [3]. The main problem of DPLDs in regard to the number of diagnostic units is the differential diagnosis and the limited treatment possibilities. The cornerstone to move ahead in therapeutic options is an improvement of comprehension of the immunopathogenesis
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