Reuter S, Heinz A, Sieren M, Wiewrodt R, Gelfand E W, Stassen M, Buhl R, Taube C
III. Medical Clinic, Dept of Pulmonary Medicine, University of Mainz, Mainz, Germany.
Eur Respir J. 2008 Apr;31(4):773-82. doi: 10.1183/09031936.00058907. Epub 2007 Dec 19.
Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear. In order to define the role of mast cells in acute allergic airway disease two strains of mast cell-deficient mice (Kit(W/Wv) and Kit(W-sh/W-sh)) were studied. Compared with their wild-type littermates, Kit(W/Wv) and Kit(W-sh/W-sh) mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) from wild-type mice to Kit(W-sh/W-sh) mice reconstituted both airway responsiveness and inflammation to levels similar to those in sensitised and challenged wild-type mice. In contrast, sensitised Kit(W-sh/W-sh) mice reconstituted with BMMCs from TNF-deficient mice were still severely impaired in their ability to develop airway hyperresponsiveness, inflammation or goblet cell metaplasia following allergen challenge. The present results demonstrate the significance of mast cells in the development of airway disease and highlight the importance of mast cell-derived tumour necrosis factor in these responses.
肥大细胞被认为与过敏性气道疾病有关。然而，肥大细胞产生的介质，如肿瘤坏死因子（TNF），在过敏性气道疾病发展中的作用尚不清楚。为了确定肥大细胞在急性过敏性气道疾病中的作用，研究了两种肥大细胞缺陷小鼠品系（Kit(W/Wv)和Kit(W-sh/W-sh)）。与野生型同窝小鼠相比，在无佐剂致敏和气道激发后，Kit(W/Wv)和Kit(W-sh/W-sh)小鼠对乙酰甲胆碱的气道反应性显著降低，气道炎症和杯状细胞化生也较少。将野生型小鼠的骨髓来源肥大细胞（BMMCs）转移到Kit(W-sh/W-sh)小鼠中，可使气道反应性和炎症恢复到与致敏和激发的野生型小鼠相似的水平。相反，用TNF缺陷小鼠的BMMCs重建的致敏Kit(W-sh/W-sh)小鼠在过敏原激发后，其气道高反应性、炎症或杯状细胞化生的发展能力仍然严重受损。目前的结果证明了肥大细胞在气道疾病发展中的重要性，并突出了肥大细胞来源的肿瘤坏死因子在这些反应中的重要性。
