Effect of alveolar microenvironment on biologic activity of lung fibroblast in patients with acute respiratory distress syndrome

Abstract

Objective To evaluate the effect of changes in alveolar microenvironment on lung fibroblast (LF) in patients with acute respiratory distress syndrome (ARDS). Methods Fifty-eight ARDS patients admitted to the intensive care unit (ICU) of Shaoxing People's Hospital from January 2014 to December 2016 were recruited. The patients were divided into the mild group (n=26), moderate group (n=15) and severe group (n=17) according to patients' oxygenation index and Berlin definition criteria. Another 10 patients with mechanical ventilation but no pulmonary diseases were enrolled as the control group. All patients were received bronchoalveolar lavage and the bronchial alveolar lavage fluid (BALF) was collected. The levels of interleukin-1β (IL-1β), keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) in the BALF were measured by enzyme linked immunosorbant assay (ELISA), and the protein content and cell counts in the BALF were also recorded. Lung fibroblasts (MRC-5) were cultured in vitro and co-cultured with BALF in each group. Cell migration assays were performed by the Transwell system. The expressions of CollagenⅠ and platelet-derived growth factor-receptor α (PDGF-Rα) were determined by Western-blotting. Results Compared with the control group, the levels of IL-1β [12 (8, 21), 776 (449, 943), 802 (691, 1 004), 886 (548,1 130) ng/L], KGF [2.0 (1.0, 2.2), 19.0 (15.8, 24.5), 41.4 (36.2, 57.3), 64.7 (49.2, 82.1) ng/L], HGF [90 (75, 106), 514 (373, 785), 867 (674, 1 248), 940 (660, 1 344) ng/L], the protein content [(0.09 ± 0.03), (0.29 ± 0.10), (0.45 ± 0.09), (0.68 ± 0.16) g/L] and cell counts [(2.4 ± 0.6), (16.5 ± 2.1), (17.8 ± 2.0), (18.2 ± 2.0) × 109/mL] in mild, moderate and severe groups increased significantly (Z=26.182, 55.871, 36.354; F=72.860, 177.291; all P 0.05). Compared with the control group, the cell migration assays in each ARDS subgroups were much higher (F=12.291, P=0.003), and they were highest in severe group (all P<0.05). The expressions of CollagenⅠand PDGF-Rα showed significant differneces among four groups (F=358.943, P=0.001; F=4.574, P=0.002). The expression of CollagenⅠ in each ARDS subgroups was much higher than that in the control group, and it was much higher in moderate and severe groups than in mild group (all P<0.05). The expression of PDGF-Rα increased obviously in moderate and severe groups, but it was almost absent in control and mild groups (all P<0.05). Conclusion With the aggravation of ARDS, the levels of KGF and HGF in BALF increased obviously, and the BALF in ARDS patients could induce LF migration and differentition through elevated CollagenⅠ and PDGF-Rα expressions. Key words: Respiratory distress syndrome, adult; Pulmonary alveoli; Bronchoalveolar lavage fluid; Fibroblast