Mer-mediated eosinophil efferocytosis regulates resolution of allergic airway inflammation.
J Allergy Clin Immunol
; 142(6): 1884-1893.e6, 2018 12.
Article
in En
| MEDLINE
| ID: mdl-29428392
ABSTRACT
BACKGROUND:
Eosinophils play a central role in propagation of allergic diseases, including asthma. Both recruitment and retention of eosinophils regulate pulmonary eosinophilia, but the question of whether alterations in apoptotic cell clearance by phagocytes contributes directly to resolution of allergic airway inflammation remains unexplored.OBJECTIVES:
In this study we investigated the role of the receptor tyrosine kinase Mer in mediating apoptotic eosinophil clearance and allergic airway inflammation resolution in vivo to establish whether apoptotic cell clearance directly affects the resolution of allergic airway inflammation.METHODS:
Alveolar and bone marrow macrophages were used to study Mer-mediated phagocytosis of apoptotic eosinophils. Allergic airway inflammation resolution was modeled in mice by using ovalbumin. Fluorescently labeled apoptotic cells were administered intratracheally or eosinophil apoptosis was driven by administration of dexamethasone to determine apoptotic cell clearance in vivo.RESULTS:
Inhibition or absence of Mer impaired phagocytosis of apoptotic human and mouse eosinophils by macrophages. Mer-deficient mice showed delayed resolution of ovalbumin-induced allergic airway inflammation, together with increased airway responsiveness to aerosolized methacholine, increased bronchoalveolar lavage fluid protein levels, altered cytokine production, and an excess of uncleared dying eosinophils after dexamethasone treatment. Alveolar macrophage phagocytosis was significantly Mer dependent, with the absence of Mer attenuating apoptotic cell clearance in vivo to enhance inflammation in response to apoptotic cells.CONCLUSIONS:
We demonstrate that Mer-mediated apoptotic cell clearance by phagocytes contributes to resolution of allergic airway inflammation, suggesting that augmenting apoptotic cell clearance is a potential therapeutic strategy for treating allergic airway inflammation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Hypersensitivity
/
Apoptosis
/
Eosinophils
/
C-Mer Tyrosine Kinase
/
Macrophages
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2018
Type:
Article
Affiliation country:
United kingdom