Enhanced pause correlates with airway neutrophils and airway-epithelial injury in asthmatic mice treated with dexamethasone.
OBJECTIVE
To investigate the correlations among airway inflammation, airway epithelial injury and airway hyperresponsiveness (AHR) in asthmatic mice treated with dexamethasone.


METHODS
Female BALB/c mice were sensitized with intraperitoneal and hypodermic injections of ovalbumin (OVA) and aluminum on days 0, 7 and 14, challenged with OVA starting on day 21 for 10 days, and treated with dexamethasone via intraperitoneal injection starting on day 28 for 3 days. Female C57BL/6 mice were treated intranasally with house dust mite (HDM) on days 1 and 14, challenged intranasally with HDM on days 21, 23, 25, 27 and 29, and treated with sivelestat (a selective neutrophil elastase inhibitor) via intraperitoneal injection after each challenge. Following the final challenge, enhanced pause (Penh) and differential cell counts in the broncho-alveolar lavage fluid were measured and the correlations were analyzed.


RESULTS
Compared with OVA-challenged BALB/c mice, the counterpart mice treated with dexamethasone showed reduced Penh and shedding of airway epithelial cells. In addition, we found that Penh 50 (an indicator of AHR) had positive correlations with airway neutrophils and shedding of airway epithelial cells, but no correlation with eosinophils, lymphocytes or macrophages. Moreover, shedding of airway epithelial cells had positive correlations with airway neutrophils, but no correlation with eosinophils, lymphocytes or macrophages. Further, sivelestat decreased Penh 50 and shed airway-epithelial cells in HDM-challenged C57BL/6 mice.


CONCLUSIONS
Collectively, our findings suggest that airway neutrophils and excessive shedding of airway epithelial cells, but not eosinophils, lymphocytes or macrophages, may be involved in AHR in asthmatic mice treated with dexamethasone.
['Niu|Chao|C|', 'Wang|Ting|T|', 'Zou|Wenjing|W|', 'Hu|Jie|J|', 'Ying|Linyan|L|', 'Zhang|Mingxiang|M|', 'Liu|Jingyue|J|', 'Tian|Daiyin|D|', 'Dai|Jihong|J|', 'Luo|Zhengxiu|Z|', 'Liu|Enmei|E|', 'Zou|Lin|L|', 'Xiong|Yi|Y|', 'Fu|Zhou|Z|']
D000818:Animals D000893:Anti-Inflammatory Agents D001249:Asthma D001992:Bronchoalveolar Lavage Fluid D003907:Dexamethasone D004195:Disease Models, Animal D004804:Eosinophils D005260:Female D005998:Glycine D007249:Inflammation D008214:Lymphocytes D008264:Macrophages D051379:Mice D008807:Mice, Inbred BALB C D008810:Mice, Inbred C57BL D009504:Neutrophils D010047:Ovalbumin D039981:Pyroglyphidae D020545:Respiratory Mucosa D012137:Respiratory System D013449:Sulfonamides
enhanced pause neutrophils dexamethasone airway hyperresponsiveness airway epithelium asthma