Cigarette smoke extract–treated mast cells promote alveolar macrophage infiltration and polarization in experimental chronic obstructive pulmonary disease

Abstract

Objective: Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) and may modulate the immune response of exposed individuals. Mast cell function can be altered by cigarette smoking, but the role of smoking in COPD remains poorly understood. The current study aimed to explore the role of cigarette smoke extract (CSE)-treated mast cells in COPD pathogenesis.

Methods: Cytokine and chemokine expression as well as degranulation of bone marrow-derived mast cells (BMMCs) were detected in cells exposed to immunoglobulin E (IgE) and various doses of CSE. Adoptive transfer of CSE-treated BMMCs into C57BL/6J mice was performed, and macrophage infiltration and polarization were evaluated by fluorescence-activated cell sorting (FACS). Furthermore, a coculture system of BMMCs and macrophages was established to examine macrophage phenotype transition. The role of protease serine member S31 (Prss31) was also investigated in the co-culture system and in COPD mice.

Results: CSE exposure suppressed cytokine expression and degranulation in BMMCs, but promoted the expressions of chemokines and Prss31. Adoptive transfer of CSE-treated BMMCs induced macrophage infiltration and M2 polarization in the mouse lung. Moreover, CSE-treated BMMCs triggered macrophage M2 polarization via Prss31 secretion. Recombinant Prss31 was shown to activate interleukin (IL)-13/IL-13Rα/Signal transducers and activators of transcription (Stat) 6 signaling in macrophages. Additionally, a positive correlation was found between Prss31 expression and the number of M2 macrophages in COPD mice.

Conclusion: In conclusion, CSE-treated mast cells may induce macrophage infiltration and M2 polarization via Prss31 expression, and potentially contribute to COPD progression.

• chronic objective pulmonary disease
• cigarette smoke extract
• macrophage
• M2 polarization
• mast cell
• Prss31

Acknowledgements

The experiments were performed by Hong Li, Tian Yang and Qian Ning; the study was designed by Hong Li and Zhongmin Sun; the paper was written by Feiyan Li, Tianjun Chen and Yan Yao.

Declaration of interest

The authors declare no financial conflicts of interest.