Department of Pathology, Stanford University School of Medicine, Stanford, Calif 94305-5324, USA.
J Allergy Clin Immunol. 2013 Feb;131(2):541-8.e1-9. doi: 10.1016/j.jaci.2012.05.009. Epub 2012 Jun 22.
Mast cells express receptors for complement anaphylatoxins C3a and C5a (ie, C3a receptor [C3aR] and C5a receptor [C5aR]), and C3a and C5a are generated during various IgE-dependent immediate hypersensitivity reactions in vivo. However, it is not clear to what extent mast cell expression of C3aR or C5aR influences C3a- or C5a-induced cutaneous responses or IgE-dependent mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo.
We sought to assess whether mouse skin mast cell expression of C3aR or C5aR influences (1) the cells' responsiveness to intradermal injections of C3a or C5a or (2) the extent of IgE-dependent mast cell degranulation and PCA in vivo.
We measured the magnitude of cutaneous responses to intradermal injections of C3a or C5a and the extent of IgE-dependent mast cell degranulation and PCA responses in mice containing mast cells that did or did not express C3aR or C5aR.
The majority of the skin swelling induced by means of intradermal injection of C3a or C5a required that mast cells at the site expressed C3aR or C5aR, respectively, and the extent of IgE-dependent degranulation of skin mast cells and IgE-dependent PCA was significantly reduced when mast cells lacked either C3aR or C5aR. IgE-dependent PCA responses associated with local increases in C3a levels occurred in antibody-deficient mice but not in mice deficient in FcɛRIγ.
Expression of C3aR and C5aR by skin mast cells contributes importantly to the ability of C3a and C5a to induce skin swelling and can enhance mast cell degranulation and inflammation during IgE-dependent PCA in vivo.
肥大细胞表达补体过敏毒素 C3a 和 C5a 的受体（即 C3a 受体 [C3aR] 和 C5a 受体 [C5aR]），并且 C3a 和 C5a 在体内各种 IgE 依赖性即刻过敏反应中产生。然而，肥大细胞 C3aR 或 C5aR 的表达在何种程度上影响 C3a 或 C5a 诱导的皮肤反应或体内 IgE 依赖性肥大细胞活化和被动皮肤过敏反应（PCA）尚不清楚。
我们试图评估小鼠皮肤肥大细胞 C3aR 或 C5aR 的表达是否会影响：（1）细胞对皮内注射 C3a 或 C5a 的反应性；或（2）体内 IgE 依赖性肥大细胞脱颗粒和 PCA 的程度。
我们测量了 C3a 或 C5a 皮内注射引起的皮肤反应的程度，以及 IgE 依赖性肥大细胞脱颗粒和 PCA 反应的程度，这些反应在表达 C3aR 或 C5aR 的肥大细胞或不表达 C3aR 或 C5aR 的肥大细胞中进行。
通过皮内注射 C3a 或 C5a 诱导的大部分皮肤肿胀都需要肥大细胞在该部位分别表达 C3aR 或 C5aR，当肥大细胞缺乏 C3aR 或 C5aR 时，IgE 依赖性脱颗粒和 IgE 依赖性 PCA 的程度显著降低。与 C3a 水平局部升高相关的 IgE 依赖性 PCA 反应发生在抗体缺陷型小鼠中，但在 FcɛRIγ 缺陷型小鼠中则不然。
皮肤肥大细胞表达 C3aR 和 C5aR 对 C3a 和 C5a 诱导皮肤肿胀的能力具有重要意义，并可增强体内 IgE 依赖性 PCA 时肥大细胞脱颗粒和炎症反应。
