Ghaffar O, Durham S R, Al-Ghamdi K, Wright E, Small P, Frenkiel S, Gould H J, Hamid Q
Meakins-Christie Laboratories, SMBD-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Am J Respir Cell Mol Biol. 1998 May;18(5):706-11. doi: 10.1165/ajrcmb.18.5.3030.
We have recently shown the increased mRNA expression of interleukin (IL)-4 and IL-13 in sinus biopsies from allergic subjects with chronic sinusitis (ACS), whereas only IL-13 mRNA was elevated in biopsies obtained from nonallergic subjects with chronic sinusitis (NCS). In the lymph nodes and spleen, these cytokines may promote IgE production through transcriptional activation of the germline IgE heavy chain promoter, an event which precedes immunoglobulin isotype switching to IgE in B cells. We hypothesized that local expression of IL-4 and/or IL-13 might act by inducing germline IgE heavy chain transcript expression locally in the sinus mucosa of chronic sinusitis patients. Mucosal sinus biopsies were obtained from 13 patients with ACS, 12 subjects with NCS, and 11 normal control individuals. The numbers of B cells in the sinus mucosa were studied by immunocytochemistry with anti-CD20 monoclonal antibodies. In situ hybridization was performed using antisense radiolabeled riboprobes complementary to the IgE epsilon -heavy chain germline (Iepsilon) and heavy chain constant region (Cepsilon) gene transcripts. Riboprobes specific for the IgG gamma-heavy chain constant region (Cgamma) were used as an isotype control. Immunocytochemical analysis indicated augmented numbers of CD20-positive B cells in the biopsies obtained from ACS patients compared with NCS subjects (P < 0.05) and normal control subjects (P < 0.01). Statistically significant increases were observed in the numbers of cells expressing Iepsilon and Cepsilon transcripts in the sinus mucosa of ACS patients compared with those with NCS (P < 0. 001) and normal controls (P < 0.001), while Cgamma RNA expression did not differ significantly between the groups. In three randomly selected ACS biopsies, 92-100% of cells expressing Cepsilon transcripts and 100% of Iepsilon RNA-positive cells coexpressed CD20 immunoreactivity. Cells expressing Cepsilon transcripts were also significantly increased in NCS compared with normal controls (P < 0. 05). The results of this study suggest that local IgE class switching occurs in the pathogenesis of ACS and that ACS and NCS are both associated with increased expression of Cepsilon transcripts.
我们最近发现，在患有慢性鼻窦炎的变应性受试者（ACS）的鼻窦活检组织中，白细胞介素（IL）-4和IL-13的mRNA表达增加，而在患有慢性鼻窦炎的非变应性受试者（NCS）的活检组织中，只有IL-13 mRNA升高。在淋巴结和脾脏中，这些细胞因子可通过种系IgE重链启动子的转录激活来促进IgE的产生，这一事件发生在B细胞中免疫球蛋白同种型转换为IgE之前。我们推测，IL-4和/或IL-13的局部表达可能通过在慢性鼻窦炎患者的鼻窦黏膜中局部诱导种系IgE重链转录本表达而起作用。从13例ACS患者、12例NCS受试者和11名正常对照个体获取鼻窦黏膜活检组织。用抗CD20单克隆抗体通过免疫细胞化学研究鼻窦黏膜中B细胞的数量。使用与IgEε-重链种系（Iε）和重链恒定区（Cε）基因转录本互补的反义放射性标记核糖探针进行原位杂交。用于IgGγ-重链恒定区（Cγ）的特异性核糖探针用作同种型对照。免疫细胞化学分析表明，与NCS受试者（P<0.05）和正常对照受试者（P<0.01）相比，从ACS患者获得的活检组织中CD20阳性B细胞数量增加。与NCS患者（P<0.001）和正常对照（P<0.001）相比，观察到ACS患者鼻窦黏膜中表达Iε和Cε转录本的细胞数量有统计学意义的增加，而各组之间Cγ RNA表达无显著差异。在随机选择的3例ACS活检组织中，92%-100%表达Cε转录本的细胞和100%的Iε RNA阳性细胞共表达CD20免疫反应性。与正常对照相比，NCS中表达Cε转录本的细胞也显著增加（P<0.05）。本研究结果表明，局部IgE类别转换发生在ACS的发病机制中，并且ACS和NCS均与Cε转录本表达增加有关。
