Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilon RI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells

Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilon RI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells
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DOI:
10.1172/jci119311
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发表时间:
1997-04-01
影响因子:
15.9
通讯作者:
Ra, CS
Ra, CS
中科院分区:
医学1区
文献类型:
--
作者:
Pawankar, R;Okuda, M;Ra, CS

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与肥大细胞表面上的高亲和力IgE受体(Fc IgE RI)结合的过敏原特异性IEE与多价过敏原的交联导致预先形成的和新产生的介质的释放,以及过敏症状的表现。因此,Fc β RI的表达和IgE的合成对于变应性疾病的发展至关重要。在这项研究中,我们报告了与慢性感染性鼻炎(CIR)患者的鼻肥大细胞(NMC)相比,常年性变应性鼻炎(PAR)患者的鼻肥大细胞(NMC)表达显著更高水平的Fc β RI、CD 40 L、IL-4和IL-13,PAR患者PBMC中Fc ε RI表达水平与血清总IgE(r = 0.89,P <0.0004)和特异性IgE(r = 0.88,P <0.003)水平呈显著正相关。此外,通过流式细胞术和逆转录酶-聚合酶链反应检测,用IL-4刺激NMC,在蛋白质和mRNA水平上上调Fc β RI α链表达。此外,在Der fII(螨抗原)存在的情况下,PAR患者的NMC(而非CIR患者)诱导纯化的B细胞合成IgE。这些结果表明,肥大细胞在促进过敏反应,通过增加表达的Fc ε RI和增强和放大IgE的生产,在当地的微环境中的新的和关键的作用。
Cross-linking of allergen specific IEE bound to the high affinity IgE receptor (Fc epsilon RI) on the surface of mast cells with multivalent allergens results in the release of both preformed and newly generated mediators, and in the manifestation of allergic symptoms. The expression of Fc epsilon RI, and the synthesis of IgE are therefore critical for the development of allergic diseases, In this study, we report that nasal mast cells (NMC) from patients with perennial allergic rhinitis (PAR) expressed significantly greater levels of the Fc epsilon RI, CD40L, IL-4, and IL-13 as compared to NMC from patients with chronic infective rhinitis (CIR), The level of Fc epsilon RI expression in NMC of PAR patients strongly correlated with the levels of serum total (r = 0.8, P < 0.003) and specific IgE (r = 0.89, P < 0.0004) antibodies. In addition, stimulation of NMC with IL-4, upregulated the Fc epsilon RI alpha chain expression both at the protein and mRNA levels, as detected by now cytometry and reverse transcriptase-polymerase chain reaction. Furthermore, NMC from PAR, but not CIR, patients induced IgE synthesis by purified B cells in the presence of Der fII (mite antigen). These results suggest novel and critical roles for mast cells in promoting the allergic reaction through the increased expression of Fc epsilon RI and by enhancing and amplifying the IgE production, within the local microenvironment.