LPS exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea pig model of asthma.
LPS exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea pig model of asthma.
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DOI：
10.1111/bph.13080
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发表时间：
2015-05
影响因子：
7.3
通讯作者：
Ford WR
中科院分区：
文献类型：
--
作者：
Lowe AP;Thomas RS;Nials AT;Kidd EJ;Broadley KJ;Ford WR
哮喘加重会导致皮质类固醇不敏感。LP在环境中无处不在。它会引起支气管收缩和呼吸道炎症，因此可能会加剧过敏原反应。本研究探讨了内毒素和卵清蛋白联合应用能否加重清醒豚鼠对卵清蛋白引起的呼吸道炎症反应和功能反应，以及吸入丙酸氟替卡松(FP)后这些加重反应是否不敏感。用卵白蛋白致敏和激发豚鼠，用全身体积描记法记录其比导气量。从肺组织学和支气管肺泡灌洗检测气道炎症。卵清蛋白后24 h检测吸入性组胺的高反应性。在卵白蛋白前24或48 单独吸入脂多糖，并与卵白蛋白联合吸入。FP(0.0 5-1 mg·m L−1)或赋形剂雾化吸入15 m in，每日2次，连续6 d。吸入卵清蛋白可引起早期(EAR)和晚期哮喘反应(LAR)、呼吸道对组胺的高反应性和炎症细胞进入肺部。48 h前给予脂多糖和卵清蛋白联合给药后，随着耳长的增加，对组胺的反应时间延长，炎性细胞增多，反应加重。FP-0.5和1 mg·mLLPS-1可显著降低−-1对卵白蛋白作用下的细胞内流和细胞内流，但对卵蛋白作用前后的豚鼠细胞内流无明显影响。脂多糖暴露加剧了吸入性过敏原引起的呼吸道炎症和功能反应，降低了皮质类固醇的敏感性。它在环境中的广泛存在可能会导致人类哮喘加重和皮质类固醇不敏感。
Asthma exacerbations contribute to corticosteroid insensitivity. LPS is ubiquitous in the environment. It causes bronchoconstriction and airway inflammation and may therefore exacerbate allergen responses. This study examined whether LPS and ovalbumin co-administration could exacerbate the airway inflammatory and functional responses to ovalbumin in conscious guinea pigs and whether these exacerbated responses were insensitive to inhaled corticosteroid treatment with fluticasone propionate (FP). Guinea pigs were sensitized and challenged with ovalbumin and airway function recorded as specific airway conductance by whole body plethysmography. Airway inflammation was measured from lung histology and bronchoalveolar lavage. Airway hyper-reactivity (AHR) to inhaled histamine was examined 24 h after ovalbumin. LPS was inhaled alone or 24 or 48 h before ovalbumin and combined with ovalbumin. FP (0.05–1 mg·mL−1) or vehicle was nebulized for 15 min twice daily for 6 days before ovalbumin or LPS exposure. Ovalbumin inhalation caused early (EAR) and late asthmatic response (LAR), airway hyper-reactivity to histamine and influx of inflammatory cells into the lungs. LPS 48 h before and co-administered with ovalbumin exacerbated the response with increased length of the EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and 1 mg·mL−1 reduced the LAR, AHR and cell influx with ovalbumin alone, but was ineffective when guinea pigs were exposed to LPS before and with ovalbumin. LPS exposure exacerbates airway inflammatory and functional responses to allergen inhalation and decreases corticosteroid sensitivity. Its widespread presence in the environment could contribute to asthma exacerbations and corticosteroid insensitivity in humans.
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DOI：
10.1016/j.jaci.2008.07.007
发表时间：
2008-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Goleva E;Hauk PJ;Hall CF;Liu AH;Riches DW;Martin RJ;Leung DY
通讯作者：
Leung DY
影响因子：
7.3
作者：
Alexander SP;Benson HE;Faccenda E;Pawson AJ;Sharman JL;Spedding M;Peters JA;Harmar AJ;CGTP Collaborators
通讯作者：
CGTP Collaborators
影响因子：
7.3
作者：
Alexander SP;Benson HE;Faccenda E;Pawson AJ;Sharman JL;Spedding M;Peters JA;Harmar AJ;CGTP Collaborators
通讯作者：
CGTP Collaborators
影响因子：
6.1
作者：
Komlosi, Z. I.;Pozsonyi, E.;Losonczy, G.
通讯作者：
Losonczy, G.
DOI：
10.1152/ajplung.1996.270.5.l736
发表时间：
1996-05-01
影响因子：
4.9
作者：
Dubin, W;Martin, TR;Hasday, JD
通讯作者：
Hasday, JD