Abnormal neutrophil polarization in chronic obstructive pulmonary disease and how cigarette smoke extracts attract neutrophils

Fan Deng; Shaobo Zhong; Changhui Yu; Haijin Zhao; Hui Huang; Xiaojing Meng; Changqin Lin; Shaoxi Cai

doi:10.21037/atm-22-1480

Abnormal neutrophil polarization in chronic obstructive pulmonary disease and how cigarette smoke extracts attract neutrophils

Ann Transl Med. 2022 Apr;10(8):472. doi: 10.21037/atm-22-1480.

Authors

Fan Deng^{1

2}, Shaobo Zhong³, Changhui Yu², Haijin Zhao², Hui Huang¹, Xiaojing Meng⁴, Changqin Lin¹, Shaoxi Cai²

Affiliations

¹ Department of Respiratory Medicine, Huizhou Municipal Central Hospital, Huizhou, China.
² Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
³ Department of Peripheral Vascular Intervention, Huizhou Municipal Central Hospital, Huizhou, China.
⁴ Department of Occupational Health and Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.

Abstract

Background: Airway inflammation produced by neutrophils is a critical factor in the development of chronic obstructive pulmonary disease (COPD). Poor or excessive neutrophil polarization and chemotaxis may lead to pathogen accumulation and tissue damage. However, it is unclear how cigarette smoke extract (CSE) attracts neutrophils and to what extent COPD is affected by the improper polarization of these abnormal neutrophils. This study sought to assess the polarization and migration dynamics of neutrophils isolated from patients with different severities of COPD compared to healthy smoking and non-smoking control subjects, and to detect how CSE triggers the polarization of neutrophils.

Methods: The neutrophils were freshly isolated using standard isolation protocol. The polarization of the neutrophils was observed using a Zigmond chamber when stimulated by a linear concentration gradient of CSE or N-formyl-methionine-leucine-phenylalanine (fMLP). Confocal laser-scanning microscopy was used to observe the intracellular calcium of the neutrophils. The experimental data are presented as the mean ± standard deviation. SPSS 20.0 software was used for the statistical analysis. A P value <0.05 was considered statistically significant.

Results: The neutrophils from the COPD patients showed a higher frequency of spontaneous polarization and a lower prevalence of directionality polarization than those from the healthy control (HC) and smoker subjects. The abnormal polarization of the neutrophils from the COPD patients was altered by the influence of store-operated calcium entry (SOCE) component matrix interaction molecules 1 and 2 and calcium release-activated calcium channel protein 1 [stromal interaction molecule 1 (STIM1), Stromal interaction molecule 2 (STIM2), and calcium release-activated calcium modulator 1 (ORAI1)].

Conclusions: The COPD neutrophils exhibited unique polarization and migration patterns compared to those of the cells examined from other populations. The attraction of CSEs to neutrophils was mediated by the SOCE/Akt/Src pathway.

Keywords: Chronic obstructive pulmonary disease (COPD); cigarette smoke extract (CSE); neutrophil polarization; store-operated calcium entry (SOCE).