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Syk mediates airway contractility independent of leukocyte function
Author(s) -
Wang X.,
Khan.,
Wu J.,
Godri Pollitt K.,
Evans G. J.,
Chow C.W.,
Scott J. A.
Publication year - 2015
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12564
Subject(s) - syk , bronchoalveolar lavage , medicine , respiratory system , immunology , inflammation , contractility , lung , receptor , tyrosine kinase
Background Syk, an immune regulatory tyrosine kinase, plays a role in inflammatory disease processes. We recently reported a role for epithelial expression of Syk in the airways hyper‐responsiveness in response to air pollution in a mouse model of asthma. The aim of this study was to further investigate the role of Syk in airway contractility in response to methacholine ( MC h) and particulate matter ( PM ) air pollutants, in the absence of underlying inflammation. Methods We used Syk flox/flox //rosa26Cre ER T 2 conditional Syk knockout mice to evaluate respiratory mechanics and MC h responsiveness following PM exposure in vivo using the ventilator‐based flexiVent ® system. Results While total and differential cell counts in bronchoalveolar lavage fluid were similar between the Syk flox/flox and Syk del/del mice, central airways respiratory resistance ( R N ) to MC h was significantly augmented following PM exposure between Syk‐intact (Syk flox/flox ) and Syk‐deficient (Syk del/del ) mice ( R N (max) : 2.06 ± 0.29 vs. 1.29 ± 0.10, respectively; p < 0.05, n = 8–10/group). We employed live videomicroscopy to investigate changes in airway luminal diameter using ex vivo lung slices, which were devoid of circulating leukocytes. MC h reduced the airway luminal area of Syk flox/flox mice to 81.1 ± 1.4% of baseline, which was virtually abrogated in Syk del/del mice (luminal area = 93.2 ± 0.5%, n = 5/group, p < 0.05). In response to PM exposure, Syk flox/flox airways contracted to 73.8 ± 2.7% of baseline luminal diameter, whereas Syk del/del airways exhibited minimal contractility to PM and MC h (90.0 ± 1.3% of baseline, n = 5/group, p < 0.05). Conclusions These observations suggest that Syk mediates airway contractility in the normal and allergic airways, independent of its role and function in leukocytes, and supports a paracrine role for airway epithelial Syk in modulating airway smooth muscle activity.