Murakami D, Yamada H, Yajima T, Masuda A, Komune S, Yoshikai Y
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Clin Exp Allergy. 2007 Mar;37(3):339-47. doi: 10.1111/j.1365-2222.2006.02633.x.
Bacterial infection occasionally exacerbates asthma, although the cellular and molecular mechanisms have not been well defined. An involvement of mast cells has been suggested, as lipopolysaccharides (LPS)-induced cytokine production from mast cells in vitro.
This study was undertaken to examine the effects of LPS inhalation on mast cell functions and allergen-specific immune responses in a murine model of asthma.
Female BALB/c mice or mast cell-deficient W/W(v) mice were immunized intraperitoneally with ovalbumin (OVA). Mice were challenged with aerosolized OVA or OVA with LPS daily from day 21 to day 24. Twenty-four hours after the last challenge, airway inflammation and OVA-specific immune responses were examined. Allergen-specific T cell responses were further analysed by adoptively transferring OVA-specific CD4(+) T cells. Expression of chemokines in the lung was also examined.
LPS inhalation with OVA resulted in exacerbated airway infiltration, which was not evident in mast cell-deficient mice. IL-5 production by mast cells in the lung was enhanced by LPS inhalation. OVA-specific IgE production as well as proliferation, cytokine production and local infiltration of OVA specific T-helper lymphocytes type 2 (Th2) were also enhanced. Up-regulated expression of Th2- and/or eosinophil-attracting chemokines was observed in the lung of mice inhalated with LPS.
LPS inhalation exacerbates airway inflammation, which is accompanied by mast cell activation and enhanced Th2 responses. These observations provide clues towards understanding the mechanisms of bacterial infection-induced exacerbation of the clinical features of asthma.
细菌感染偶尔会加重哮喘，尽管其细胞和分子机制尚未完全明确。由于脂多糖（LPS）可在体外诱导肥大细胞产生细胞因子，因此提示肥大细胞参与其中。
本研究旨在探讨在哮喘小鼠模型中吸入LPS对肥大细胞功能和变应原特异性免疫反应的影响。
雌性BALB/c小鼠或肥大细胞缺陷型W/W(v)小鼠腹腔注射卵清蛋白（OVA）进行免疫。从第21天至第24天，每天用雾化的OVA或OVA加LPS对小鼠进行激发。最后一次激发后24小时，检测气道炎症和OVA特异性免疫反应。通过过继转移OVA特异性CD4(+) T细胞进一步分析变应原特异性T细胞反应。还检测了肺中趋化因子的表达。
吸入OVA加LPS导致气道浸润加剧，这在肥大细胞缺陷型小鼠中不明显。吸入LPS可增强肺中肥大细胞产生IL-5。OVA特异性IgE的产生以及OVA特异性2型辅助性T淋巴细胞（Th2）的增殖、细胞因子产生和局部浸润也增强。在吸入LPS的小鼠肺中观察到Th2和/或嗜酸性粒细胞趋化因子的表达上调。
吸入LPS会加重气道炎症，同时伴有肥大细胞活化和Th2反应增强。这些观察结果为理解细菌感染诱发哮喘临床症状加重的机制提供了线索。
