Premium
Dividing neutrophils in subsets reveals a significant role for activated neutrophils in the development of airway hyperreactivity
Author(s) -
Ekstedt Sandra,
Säfholm Jesper,
Georén Susanna Kumlien,
Cardell Lars Olaf
Publication year - 2019
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13311
Subject(s) - immunology , bradykinin , airway , stimulation , medicine , in vitro , receptor , asthma , downregulation and upregulation , chemistry , biochemistry , surgery , gene
Background Previous research has emphasized the importance of eosinophils in allergic asthma, while paying less attention to neutrophils. The known functionality of neutrophils in the inflammatory process has recently changed and knowledge about subsets of neutrophils, as characterized by their expression of CD 16 and CD 62L, has surfaced. Their specific roles in asthma are still unknown. Objective To study the functional differences between subsets of neutrophils by characterizing the impact of individual subsets on airway smooth muscle reactivity. Methods The direct effect of neutrophils on airway hyperresponsiveness was assessed by co‐culturing different subsets of neutrophils (produced by LPS in vitro stimulation) with human isolated small airways or murine tracheae with subsequent evaluation of smooth muscle reactivity to bradykinin in myographs. Supernatants and tissue were saved for ELISA and immunohistochemistry. Results The CD 16 high CD 62L dim neutrophils were found to enhance the response to bradykinin in both human isolated small airways and murine tracheae. No such effects were obtained for the other subsets. The response is due to an upregulation of bradykinin receptor 2 through release of TNF α from the neutrophil. Conclusions and Clinical Relevance The present study introduces a new concept regarding the role of neutrophils and defines a novel direct link between a specific activated neutrophil subset and airway smooth muscle, establishing neutrophils as important players in the development of asthmatic airway hyperactivity.