Year-end Sale % OFF 
Abstract
BackgroundControversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pulmonary disease (COPD). We hypothesized that formyl peptide receptor (FPR), a marker of efferocytosis and mediator of M1/M2 polarization, may be involved in the development of COPD.MethodsWe examined FPR 1/2/3 expressions of blood M1/M2a monocyte, neutrophil, natural killer (NK) cell, NK T cell, T helper (Th) cell, and T cytotoxic (Tc) cell by flowcytometry method in 40 patients with cigarette smoking-related COPD and 16 healthy non-smokers. Serum levels of five FPR ligands were measured by ELISA method.ResultsThe COPD patients had lower M2a percentage and higher percentages of NK, NK T, Th, and Tc cells than the healthy non-smokers. FPR2 expressions on Th/Tc cells, FPR3 expressions of M1, M2a, NK, NK T, Th, and Tc cells, and serum annexin A1 (an endogenous FPR2 ligand) levels were all decreased in the COPD patients as compared with that in the healthy non-smokers. FPR1 expression on neutrophil was increased in the COPD patient with a high MMRC dyspnea scale, while FPR2 expression on neutrophil and annexin A1 were both decreased in the COPD patients with a history of frequent moderate exacerbation (≥ 2 events in the past 1 year). In 10 COPD patients whose blood samples were collected again after 1-year treatment, M2a percentage, FPR3 expressions of M1/NK/Th cells, FPR2 expression on Th cell, and FPR1 expression on neutrophil were all reversed to normal, in parallel with partial improvement in small airway dysfunction.ConclusionsOur findings provide evidence for defective FPR2/3 and annexin A1 expressions that, associated with decreased M2a polarization, might be involved in the development of cigarette smoking induced persistent airflow limitation in COPD.
Highlights
Controversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pul‐ monary disease (COPD)
The COPD patients were older than the healthy non-smokers, but both groups were matched in co-morbidity and had a similar body mass index (BMI), glycohemoglobin (HbAc1), triglyceride, and total cholesterol level
For the first time, the present findings demonstrate that smoking-related COPD patients have diminished cell surface FPR2 expressions on helper and cytotoxic T cells, and diminished intracellular FPR3 expressions in M1 monocyte, M2a monocyte, natural killer (NK) cell, NK T cell, T helper (Th) and T cytotoxic (Tc) cells, associated with decreased blood M2a percentage and decreased serum levels of annexin A1 (ANXA1)
Summary
Controversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pul‐ monary disease (COPD). We hypothesized that formyl peptide receptor (FPR), a marker of efferocytosis and mediator of M1/M2 polarization, may be involved in the development of COPD. FPR1 has been demonstrated to be an important receptor in COPD, because genetic ablation of this receptor confers protection from the development of cigarette smoke-induced emphysema in the mouse model [7]. SAA has been shown to be a mediator of glucocorticoid-resistant lung inflammation that can overwhelm organ protective signaling by LXA4 at FPR2 receptors in a murine model of COPD [9]. Resolvin D1 (RvD1) has been reported to attenuate smoking-induced emphysema in a mouse model by reducing inflammation and promoting tissue regeneration [13] All these three ligands have been shown to contribute to resolution of inflammation through FPR2 [14]. Little is known about the role of FPR1/2/3 in the development of COPD and its clinical phenotypes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
