Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden.
J Immunol. 2012 Oct 15;189(8):3869-77. doi: 10.4049/jimmunol.1201200. Epub 2012 Sep 12.
Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c(+) cells have to be present during the challenge phase for several features of allergic inflammation to occur. Whether CD11c(+) cells play a role for Ag-induced increases of lung mast cells is unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c-diphtheria toxin receptor transgenic mice to deplete CD11c(+) cells. We demonstrate that recruitment of mast cell progenitors to the lung is substantially reduced when CD11c(+) cells are depleted during the challenge phase. This correlated with an impaired induction of endothelial VCAM-1 and led to a significantly reduced number of mature mast cells 1 wk after challenge. Collectively, these data suggest that Ag challenge stimulates CD11c(+) cells to produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung endothelium, which in turn is crucial for the Ag-induced mast cell progenitor recruitment and the increase in mast cell numbers.
患有过敏性哮喘的患者肺中有更多的肥大细胞，这可能会使症状恶化。在实验性哮喘中，在挑战阶段必须存在 CD11c(+)细胞，才能发生过敏炎症的几个特征。CD11c(+)细胞是否在 Ag 诱导的肺肥大细胞增加中发挥作用尚不清楚。在这项研究中，我们使用白喉毒素处理致敏的 CD11c-白喉毒素受体转基因小鼠以耗尽 CD11c(+)细胞。我们证明，当在挑战阶段耗尽 CD11c(+)细胞时，肥大细胞祖细胞向肺的募集大大减少。这与内皮细胞 VCAM-1 的诱导受损相关，导致挑战后 1 周成熟肥大细胞的数量显著减少。总的来说，这些数据表明，Ag 挑战刺激 CD11c(+)细胞产生细胞因子和/或趋化因子，这些因子对于肺内皮细胞上 VCAM-1 的上调是必需的，而上调 VCAM-1 对于 Ag 诱导的肥大细胞祖细胞募集和肥大细胞数量增加至关重要。
