| First Author | Wang X | Year | 2015 |
| Journal | Allergy | Volume | 70 |
| Issue | 4 | Pages | 429-35 |
| PubMed ID | 25556883 | Mgi Jnum | J:263970 |
| Mgi Id | MGI:6192926 | Doi | 10.1111/all.12564 |
| Citation | Wang X, et al. (2015) Syk mediates airway contractility independent of leukocyte function. Allergy 70(4):429-35 |
| abstractText | 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 (MCh) and particulate matter (PM) air pollutants, in the absence of underlying inflammation. METHODS: We used Syk(flox/flox) //rosa26CreER(T) (2) conditional Syk knockout mice to evaluate respiratory mechanics and MCh 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 (RN ) to MCh was significantly augmented following PM exposure between Syk-intact (Syk(flox/flox) ) and Syk-deficient (Syk(del/del) ) mice (RN (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. MCh 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 MCh (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. |
