Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide.
Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide.
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DOI：
10.1165/ajrcmb.22.5.3710
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发表时间：
2000-05
影响因子：
6.4
通讯作者：
Meri K. Tuli;J. Wale;P. Holt;P. Sly
中科院分区：
文献类型：
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作者：
Meri K. Tuli;J. Wale;P. Holt;P. Sly
呼吸道感染在改变特应性和哮喘发展中的潜在作用是复杂的。研究表明，感染可有效预防生命早期诱导 T 辅助细胞 2 极化过敏原特异性免疫，但也会加剧老年敏感个体的哮喘。这些影响背后的机制尚不清楚。这项工作的目的是确定脂多糖 (LPS) 暴露对过敏原致敏发展和体内过敏原激发反应的影响。 Piebald-Virol-Glaxo 大鼠在卵清蛋白 (OVA) 致敏前 1 天或致敏后 1、2、4、6、8 或 10 天暴露于单一 LPS 气雾剂。第11天，动物暴露于1% OVA，24小时后测量对过敏原的反应，使用强制振荡技术监测炎症细胞流入和支气管肺泡灌洗（BAL）液中的微血管渗漏以及肺部对乙酰甲胆碱的反应。组织学分析是为了补充 BAL 结果。腹腔注射 OVA 前 1 天和注射后 4 天单次气溶胶暴露于 LPS，可防止 OVA 特异性免疫球蛋白 (Ig) E 的形成。致敏后 6、8 或 10 天的 LPS 暴露进一步加剧 OVA 诱导的细胞内流，导致中性粒细胞增多和伊文思蓝染料渗漏增加，但对血清 IgE 水平没有影响。此外，在 OVA 攻击后 18 小时给予 LPS，可消除致敏动物中 OVA 诱导的高反应性。这项研究表明，接触 LPS 可以通过两种独立的机制改变体内过敏性炎症的发展。在致敏过程的早期，即接触过敏原后第 6 天，可以防止过敏原致敏。致敏动物在过敏原激发后暴露于 LPS 消除了高反应性，并改变了对过敏原的晚期反应的炎症细胞流入特征。
The potential role of respiratory infections in altering the development of atopy and asthma is complex. Infections have been suggested to be effective in preventing the induction of T-helper 2-polarized allergen-specific immunity in early life, but also to exacerbate asthma in older, sensitized individuals. The mechanism(s) underlying these effects are poorly defined. The aim of this work was to determine the influence of lipopolysaccharide (LPS) exposure on the development of sensitization to allergen and the response to allergen challenge in vivo. Piebald-Virol-Glaxo rats were exposed to a single aerosol of LPS 1 d before or 1, 2, 4, 6, 8, or 10 d after sensitization with ovalbumin (OVA). On Day 11 animals were exposed to 1% OVA and responses to allergen were measured 24 h later, monitoring inflammatory cell influx and microvascular leakage into bronchoalveolar lavage (BAL) fluid as well as pulmonary responses to methacholine using the forced oscillation technique. Histologic analysis was included to complement the BAL results. Single aerosol exposure to LPS 1 d before and up to 4 d after intraperitoneal injection of OVA protected against the development of OVA-specific immunoglobulin (Ig) E. LPS exposure 6, 8, or 10 d after sensitization further exacerbated the OVA-induced cellular influx, resulting in neutrophilia and increased Evans Blue dye leakage with no effect on serum IgE levels. In addition, LPS abolished the OVA-induced hyperresponsiveness in sensitized animals when given 18 h after OVA challenge. This study demonstrates that exposure to LPS can modify the development of allergic inflammation in vivo by two independent mechanisms. Exposure early in the sensitization process, up to Day 6 after exposure to allergen, prevented allergen sensitization. Exposure to LPS after allergen challenge in sensitized animals abolished the hyperresponsiveness and modified the inflammatory cell influx characteristic of late-phase response to allergen.