Differential expression of C-Reactive protein and Serum amyloid A in different cell types in the lung tissue of chronic obstructive pulmonary disease patients

Abstract

BackgroundChronic systemic inflammatory syndrome has been implicated in the pathobiology of extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). We aimed to investigate which cell types within lung tissue are responsible for expressing major acute-phase reactants in COPD patients and disease-free (“resistant”) smokers.MethodsAn observational case–control study was performed to investigate three different cell types in surgical lung samples of COPD patients and resistant smokers via expression of the C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) genes. Epithelial cells, macrophages and fibroblasts from the lung parenchyma were separated by magnetic microbeads (CD326, CD14 and anti-fibroblast), and gene expression was evaluated by RT-PCR.ResultsThe sample consisted of 74 subjects, including 40 COPD patients and 34 smokers without disease. All three cell types were capable of synthesizing these biomarkers to some extent. In fibroblasts, gene expression analysis of the studied biomarkers demonstrated increased SAA2 and decreased SAA1 in patients with COPD. In epithelial cells, there was a marked increase in CRP, which was not observed in fibroblasts or macrophages. In macrophages, however, gene expression of these markers was decreased in COPD patients compared to controls.ConclusionsThese results provide novel information regarding the gene expression of CRP and SAA in different cell types in the lung parenchyma. This study revealed differences in the expression of these markers according to cell type and disease status and contributes to the identification of cell types that are responsible for the secretion of these molecules.

Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice

“…The activation of the systemic acute phase response in the liver in these studies was more limited and dependent on the type of nanomaterial and the magnitude of the lung acute phase and pro-inflammatory response. In humans, the liver is believed to be the major organ associated with acute phase reactions (Sack 2018), although SAA is also expressed in a range of normal human tissues including lung (Urieli-Shoval et al 1998;Calero et al 2014). Albeit these differences, the results from the present study suggests that mouse models can serve as the first pass screen in the investigation of particle-induced acute-phase response.…”

High-density lipoprotein inhibits serum amyloid A–mediated reactive oxygen species generation and NLRP3 inflammasome activation

“…Our finding that AngIIinduced increases in IL-1β are significantly blunted in mice lacking acute phase SAAs underscores the fact that SAA has proinflammatory effects in pathological settings, such as experimental AAA. SAA concentrations can be dramatically elevated in tissues due to local injury, infection or inflammation (15,(71)(72)(73)(74). The relative contribution of locally produced SAA versus HDL-bound SAA that has deposited in tissues at the site of injury or inflammation is not known, and merits further investigation.…”

Resolvin D1 Reduces Emphysema and Chronic Inflammation

“…44 Levels of LXA 4 and RvD1 are reduced in sputum, serum, and exhaled breath from COPD patients and serum amyloid A is increased. 43,45,46 Thus, upregulation of ALX/FPR2 expression, in combination with increased EOR and decreased LXA 4 and RvD1, could lead to increased proinflammatory signaling by serum amyloid A due to a loss of competition for receptor binding by proresolving molecules. Finally, we have also identified multiple differences in SPMs in human exhaled breath condensate between healthy volunteers and COPD patients, and demonstrated a significant decrease in RvD1 in both bronchoalveolar lavage fluid and serum from COPD patients.…”