Effect of erythromycin on the ultrastructure of human macrophages exposed to cigarette smoke extract in vitro

ABSTRACT

Macrophages serve an active role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been verified as an effective treatment for COPD. However, there are few studies on the effect of EM on the ultrastructure of macrophages exposed to cigarette smoke extract (CSE). In the present study, human macrophages were randomly divided into three groups: The control, CSE and the CSE+EM group, using electron microscopy, the effect of EM was evaluated by comparing the ultrastructural changes between these groups. The macrophages were additionally divided into a further four groups: The control, CSE, CSE+EM 24 h and CSE+EM 48 h groups. The generation of reactive oxygen species (ROS) in each group was evaluated by detecting fluorescence intensity. It was observed that the cellular ultrastructure of the CSE group exhibited abnormal changes, though this effect was reversed back to the level of the control in the CSE+EM group. Compared with the control group, the ROS expression level was significantly increased in the CSE group (P < .05); however, compared with the CSE group, the ROS concentration was decreased in the CSE+EM 24 h (P < .05) and CSE+EM 48 h groups (P < .05), though this was more apparent in the EM 48 h group. It was concluded that EM protects human macrophages against CSE. Moreover, it was hypothesized that EM may reduce the symptoms of patients with COPD by protecting the macrophage ultrastructure from the effects of CSE, resulting in the decreased generation of ROS, inhibiting autophagy and reducing endoplasmic reticulum stress.

KEYWORDS:

• Erythromycin
• cigarette smoke extract
• human macrophages
• ultrastructure
• reactive oxygen species

Abbreviation

Chronic obstructive pulmonary disease (COPD); Erythromycin (EM); cigarette smoke extract (CSE); reactive oxygen species (ROS); tumor necrosis factor-a (TNF)-a; interleukin (IL); nuclear factor-κB (NF-κB); optical density(Od); Phosphate Buffer solution (PBS); endoplasmic reticulum (ER); Autophagy‐related gene 4 (ATG4); hypoxia-inducible factor-1α(Hif-1 α); mammalian target of rapamycin (MTOR); Mitogen-activated protein kinase (MAPK); transmission electron microscopy (TEM); nuclear membrane (NM); ER stress (ERS);

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The present study was supported by the National Natural Science Foundation of China (81360012) and Natural Science Foundation of Guangxi Zhuang Autonomous Region (2016GXNSFAA380269) and Innovation Project of Guangxi Graduate Education（JGY2019051). The funders were not involved in the study design, data collection and analysis, decision to publish, or the preparation of the manuscript.