Department of Pulmonary Medicine, Third Medical Clinic, Johannes Gutenberg University Mainz, Mainz, Germany.
Int Arch Allergy Immunol. 2010;151(3):214-22. doi: 10.1159/000242359. Epub 2009 Sep 29.
The migration of dendritic cells (DCs) from the lungs to the regional lymph nodes is necessary for the development of allergic airway disease. Following activation, mast cells release a variety of stored or de novo-produced inflammatory mediators, several of them being capable of activating DCs. In this study, the role of mast cells on DC migration from the lungs to the thoracic lymph nodes was investigated in sensitized mice.
Mast cell-deficient mice (Kit(W-sh/W-sh)) and their wild-type counterparts were sensitized intraperitoneally with ovalbumine (OVA) in saline and challenged by a single intranasal administration of OVA labeled with a fluorescent dye (OVA-Alexa).
Following challenge, the relative and absolute amount of OVA- Alexa-positive DCs was clearly increased in sensitized wild-type mice compared to nonsensitized mice. In contrast, sensitized Kit(W-sh/W-sh) showed no increase in OVA-Alexa-positive DCs compared to nonsensitized mast cell-deficient animals. In sensitized Kit(W-sh/W-sh) mice reconstituted with bone marrow-derived mast cells (BMMCs), the number of OVA- Alexa-positive DCs was comparable to that in sensitized wild-type animals. However, transfer of allergen-exposed BMMCs to sensitized mice prior to airway challenge augmented airway inflammation similarly in wild-type and mast cell-deficient mice. In line with this, sensitization with allergen-pulsed DCs induced allergic airway disease independently of mast cells.
This study shows an interaction between mast cells and DCs following allergen challenge in sensitized hosts. However, the function of mast cells can be bypassed in models utilizing activated allergen-exposed DCs to initiate the development of allergic airway disease.
树突状细胞（DCs）从肺部迁移到区域淋巴结对于过敏性气道疾病的发展是必要的。在激活后，肥大细胞释放各种储存或新合成的炎症介质，其中几种能够激活 DCs。在这项研究中，研究了致敏小鼠中肥大细胞对 DC 从肺部迁移到胸淋巴结的作用。
用卵清蛋白（OVA）在生理盐水中对肥大细胞缺陷型小鼠（Kit（W-sh/W-sh））及其野生型对照进行腹腔内致敏，并通过单次鼻腔内给予荧光标记的 OVA（OVA-Alexa）进行挑战。
与未致敏小鼠相比，致敏野生型小鼠在挑战后 OVA-Alexa 阳性 DC 的相对和绝对数量明显增加。相比之下，致敏 Kit（W-sh/W-sh）与未致敏肥大细胞缺陷型动物相比，OVA-Alexa 阳性 DC 没有增加。在致敏 Kit（W-sh/W-sh）小鼠中用骨髓来源的肥大细胞（BMMCs）重建时，OVA-Alexa 阳性 DC 的数量与致敏野生型动物相当。然而，在气道挑战之前将暴露于过敏原的 BMMCs 转移至致敏小鼠中，会在野生型和肥大细胞缺陷型小鼠中同样增强气道炎症。与此一致，用致敏抗原脉冲的 DCs 致敏会独立于肥大细胞引发过敏性气道疾病。
这项研究表明，在致敏宿主中，过敏原挑战后肥大细胞和 DCs 之间存在相互作用。然而，在利用激活的暴露于过敏原的 DCs 来启动过敏性气道疾病发展的模型中，可以绕过肥大细胞的功能。
