Abstract
Platelet-activating factor (PAF) is essentially involved in inflammation and fibrosis. However, the clinical implication of PAF in tuberculous pleural effusion (TBPE) remains unknown. The effusion PAF levels were measured among 65 patients including transudative pleural effusion (TPE, n=25) and TBPE (n=40) groups. Pleural fibrosis, defined as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Additionally, the expression of PAF and PAF receptor (PAFR) in pleural mesothelial cells (PMCs) and the effects of PAF on mesothelial mesenchymal transition (MMT) and extracellular matrix (ECM) producion were assessed in vitro and in vivo. The median PAF levels were markedly elevated in TBPE, as compared with TPE (56.6 vs. 5.2 ng/mL, p<0.0001). Effusion PAF were significantly higher in TBPE patients with RPT >10 mm (n=10) than those with RPT ≤10 mm (n=30) (319.9 vs. 28.8 ng/mL, p<0.0001), and correlated substantially with the area of residual pleural shadowing (r=0.72, p<0.001). In PMCs, Mycobacterium tuberculosis H37Ra significantly induced PAF protein synthesis and PAFR gene expression. Both PAF and bleomycin concentration-dependently stimulated MMT with upregulation of Snail and α-smooth muscle actin, and elicited ECM overproduction; consistently, the PAFR inhibitor rupatadine effectively abrogated these effects. Furthermore, compared to controls, carbon black/bleomycin treatment substantially induced PAF and PAFR expression in the areas of pleura and subpleural fibrosis in vivo. Collectively, PAF upregulates MMT and ECM and correlates with tuberculous pleural fibrosis. PAF/PAFR inhibition may confer potential therapy for fibrotic pleural diseases.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3356.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020