title: 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.
  
  
  CONCLUSIONS
  In conclusion, CSE-treated mast cells may induce macrophage infiltration and M2 polarization via Prss31 expression, and potentially contribute to COPD progression.
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ning
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Li
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Chen
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D045424:Complex Mixtures / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D062789:Tobacco Products / Q000009:adverse effects* / Q000032:analysis; D053802:Tryptases / Q000235:genetics / Q000378:metabolism
chemical_list: D045424:Complex Mixtures; D016207:Cytokines; D011994:Recombinant Proteins; D012906:Smoke; D053802:Tryptases; C000592404:Tpsg1 protein, Mouse
keywords: M2 polarization; Prss31; chronic objective pulmonary disease; cigarette smoke extract; macrophage; mast cell