Defective formyl peptide receptor 2/3 and annexin A1 expressions associated with M2a polarization of blood immune cells in patients with chronic obstructive pulmonary disease

• Published in: Journal of translational medicine Vol. 16; no. 1; p. 69
• Main Authors: Chen, Yung-Che, Lin, Meng-Chih, Lee, Chih-Hung, Liu, Shih-Feng, Wang, Chin-Chou, Fang, Wen-Feng, Chao, Tung-Ying, Wu, Chao-Chien, Wei, Yu-Feng, Chang, Huang-Chih, Tsen, Chia-Cheng, Chen, Hung-Chen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.03.2018; BioMed Central; BMC
• Subjects: Annexin A1; Annexin A1 - blood; Annexins; Blood cells; Care and treatment; Case-Control Studies; Cell Polarity; Cellular signal transduction; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarette smoking; Disease Progression; Formyl peptide receptor 1/2/3; Gene expression; Genetic aspects; Humans; Ligands; M2a polarization; Macrophages - metabolism; Macrophages - pathology; Middle Aged; Phenotype; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - pathology; Receptors, Formyl Peptide - blood; Chronic obstructive pulmonary disease; Formyl peptide receptor 1/2/3; M2a polarization; Annexin A1; Cigarette smoking
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1435-5

Controversy 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. We 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. The 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. Our 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.