Brightling C E, Symon F A, Holgate S T, Wardlaw A J, Pavord I D, Bradding P
Institute for Lung Health, Leicester-Warwick Medical School and University Hospitals of Leicester, Leicester, UK.
Clin Exp Allergy. 2003 Dec;33(12):1711-6. doi: 10.1111/j.1365-2222.2003.01827.x.
Airway smooth muscle infiltration by mast cells is a feature of asthma and not eosinophilic bronchitis. In asthma, Th2 cytokines have been implicated as playing a critical role in the development of airway inflammation and hyper-responsiveness. Whether inflammatory cells within the airway smooth muscle release these cytokines is unknown.
We have undertaken a comparative immunohistochemical study in bronchial biopsies from 14 subjects with asthma, 10 with eosinophilic bronchitis and eight normal controls recruited from two centres.
The median number of IL-4+ cells/mm2 smooth muscle was significantly higher in subjects with asthma than eosinophilic bronchitis and normal controls for both the anti-IL-4 mAb 3H4 (2.4, 0, 0, respectively; P=0.001) and anti-IL-4 mAb 4D9 (1.6, 0, 0, respectively; P=0.02). There were no group differences in the number of IL-5+ cells (P=0.31). In six subjects with asthma, IL-13 expression by cells within the airway smooth muscle was studied. The median (range) of IL-13+cells was 2 (0.9-2.7). Ninety-four percent of the cells expressing IL-4 (3H4), 92% of those expressing IL-4 (4D9) and 100% expressing IL-13 in the airway smooth muscle were mast cells. Fifty-five percent of the mast cells within the airway smooth muscle co-localized to IL-4 (3H4), 29% to IL-4 (4D9) and 17% to IL-13.
In asthma, IL-4+ and IL-13+ cells were present within the airway smooth muscle and were expressed predominantly by mast cells, suggesting that IL-4 and IL-13 may play an important role in mast cell-airway smooth muscle interactions.
肥大细胞浸润气道平滑肌是哮喘而非嗜酸性粒细胞性支气管炎的一个特征。在哮喘中,Th2细胞因子被认为在气道炎症和高反应性的发展中起关键作用。气道平滑肌内的炎症细胞是否释放这些细胞因子尚不清楚。
我们对来自两个中心招募的14例哮喘患者、10例嗜酸性粒细胞性支气管炎患者和8例正常对照者的支气管活检组织进行了比较免疫组织化学研究。
对于抗IL-4单克隆抗体3H4(分别为2.4、0、0;P=0.001)和抗IL-4单克隆抗体4D9(分别为1.6、0、0;P=0.02),哮喘患者气道平滑肌中IL-4+细胞/mm2的中位数显著高于嗜酸性粒细胞性支气管炎患者和正常对照者。IL-5+细胞数量无组间差异(P=0.31)。对6例哮喘患者气道平滑肌内细胞的IL-13表达进行了研究。IL-13+细胞的中位数(范围)为2(0.9-2.7)。气道平滑肌中表达IL-4(3H4)的细胞中有94%、表达IL-4(4D9)的细胞中有92%以及表达IL-13的细胞中有100%是肥大细胞。气道平滑肌内55%的肥大细胞与IL-4(3H4)共定位,29%与IL-4(4D9)共定位,17%与IL-13共定位。
在哮喘中,气道平滑肌内存在IL-4+和IL-13+细胞,且主要由肥大细胞表达,提示IL-4和IL-13可能在肥大细胞-气道平滑肌相互作用中起重要作用。