Soluble CD163 is produced by monocyte-derived and alveolar macrophages, and is not associated with the severity of idiopathic pulmonary fibrosis

Abstract

The soluble form of the membrane hemoglobin scavenger receptor CD163 (sCD163), released by shedding, is a strong marker for macrophage activation. Serum sCD163 levels rise in several acute inflammatory states and some fibrosing diseases. Monocyte-derived macrophages (MoDM) differentiated by macrophage colony-stimulating factor (M-MoDM) contribute to the pathophysiology of idiopathic pulmonary fibrosis (IPF), an irreversible and rapidly fatal interstitial lung disease. Since M-MoDM express high membrane CD163 levels, we thus postulated that sCD163 could be a relevant biomarker for macrophage activation in IPF. We found that M-MoDM constitutively released higher amounts of sCD163 (49.5 ± 24.5 ng/ml) than monocytes (0.45 ± 0.32 ng/ml) or MoDM differentiated with granulocyte macrophage-stimulating factor (2.24 ± 0.98 ng/ml). The basal production of sCD163 by M-MoDM was increased following stimulation with lipopolysaccharide (123.4 ± 54.9 ng/ml) or ATP (168.9 ± 41.8 ng/ml). The sCD163 release was controlled by metalloproteases but not through ADAM17 activation. Moreover, CD163-positive macrophages and sCD163 were detected in pulmonary tissues and alveolar fluids of Caucasian patients with IPF, respectively. IPF alveolar macrophages constitutively secreted sCD163 amounts (67.6 ± 44.6 ng/µg RNA) which were significantly higher than those released by alveolar macrophages isolated from controls (19.2 ± 7.6 ng/µg RNA) or patients with other interstitial lung disease (31.5 ± 16.6 ng/µg RNA). However, the concentrations of sCD163 in blood serum collected from 155 patients with IPF did not correlate with the severity of their disease. In conclusion, our results show that M-MoDM constituted a pertinent model to study the regulation of sCD163 production. Yet, serum sCD163 values could not provide a prognostic biomarker for IPF in our cohort.

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

“…CHIT1 [73], EGR1 [74], S100A12 [75], CD163 [76] and S100A8 [77] have a critical role in initiating COPD. CHIT1 [78], EGR1 [79], ATF3 [80], S100A12 [81], CD163 [82] and S100A8 [81] were significantly associated with idiopathic pulmonary fibrosis. CHIT1 [83], EGR1 [84], ATF3 [85], XIST (X inactive specific transcript) [86], CD163 [66] and S100A8 [87] level were significantly altered in obesity.…”

Plasma metabolomics profiling identifies new predictive biomarkers for disease severity in COVID-19 patients

“…Additionally, while data presented here show that the levels of sCD163 were reduced in severely ill patients, other studies have shown that sCD163 levels increase with disease severity [ 27 ]. This discrepancy could be a reflection of variations in methodology, sample collection timing, and/or differences in macrophage activity [ 28 ]. Irrespective of these discrepancies, variations in sCD163 concentration seem to have little, if any, impact on COVID-19 disease severity.…”

Equine alveolar macrophages and monocyte-derived macrophages respond differently to an inflammatory stimulus

“…However, the precise mechanisms behind this regulation remain unknown [52]. In addition to the cell membrane form, CD163 and CD206 be shed upon bacterial stimulation, generating soluble forms [53][54][55], which can be used as biomarkers for different diseases [56][57][58]. In this study, AMM and MDM responses were determined for a short interval in vitro, and the soluble forms of these proteins were not measured [11].…”