Systemic effects of allergen exposure on blood basophil IL-13 secretion and FcεRIβ
Systemic effects of allergen exposure on blood basophil IL-13 secretion and FcεRIβ
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DOI：
10.1016/j.jaci.2004.06.015
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发表时间：
2004-10-01
影响因子：
14.2
通讯作者：
Schroeder, J
中科院分区：
文献类型：
--
作者：
Saini, S;Bloom, DC;Schroeder, J
背景：气道过敏原激发研究表明，局部气道组织中细胞因子的上调以及对嗜酸性粒细胞和嗜碱性粒细胞的骨髓前体的远端影响。目的：我们研究了局部鼻内过敏原激发是否将循环嗜碱性粒细胞的表型改变为激发状态。方法：连续 3 天通过鼻内喷雾的方式对 10 名过敏性鼻炎受试者进行过敏原激发。在攻击前以及第三次过敏原攻击后3、24和96小时从受试者中分离嗜碱性粒细胞。通过蛋白质印迹法比较攻击前和最后一次过敏原攻击后的嗜碱性粒细胞的Fcis RIbeta 元件蛋白水平，并通过实时PCR 比较Fcis RIbeta 元件mRNA 表达。还比较了嗜碱性粒细胞的 IL-4 和 IL-13 自发分泌。结果：与攻击前相比，在过敏原攻击后，6 名受试者中有 5 名的嗜碱性粒细胞 Fcis RIbeta 元件蛋白水平有所增加。同样，相对于攻击前，最后一次攻击后嗜碱性粒细胞 Fcis RIbeta mRNA 水平中位数增加了 2 倍（P = .007，n = 9）。在最后一次攻击后，9 名受试者的嗜碱性粒细胞富集培养物中的 7 名受试者的上清液中检测到了 IL-13 蛋白，而攻击前的 9 名受试者中的 3 名嗜碱性粒细胞富集培养物的上清液中检测到了 IL-13 蛋白（中位数，6.2 vs 0 pg/mL；P = .058）。在任何培养物上清液中均未检测到 IL-4。结论：鼻内过敏原攻击通过增加 Fcis RIbeta 亚基元件的表达和自发的 IL-13 分泌来短暂激活循环嗜碱性粒细胞。因为Fcis（RIβ的一个元件）是Fcis（RIβ的一个元件）的放大器，并且IL-13是促炎性的，所以这些发现支持了引发的嗜碱性粒细胞的功能状态，并证明了局部过敏原攻击的全身效应，可能有助于加剧过敏反应。
Background: Airway allergen challenge studies have shown the upregulation of cytokines in local airway tissues and distal effects on bone marrow precursors for eosinophils and basophils.Objective: We investigated whether local intranasal allergen challenge alters the phenotype of circulating basophils to a primed state.Methods: Ten subjects with allergic rhinitis were challenged with allergen by means of intranasal spray on 3 sequential days. Basophils were isolated from subjects before challenge and 3, 24, and 96 hours after the third allergen challenge. Basophils were compared before challenge and after the last allergen challenge for levels of Fcis an element ofRIbeta protein by means of Western blotting and for Fcis an element ofRIbeta mRNA expression by means of realtime PCR. Basophils were also compared with regard to spontaneous secretion of IL-4 and IL-13.Results: Basophil Fcis an element ofRIbeta protein levels increased in 5 of 6 subjects after allergen challenge relative to before challenge. Likewise, basophil Fcis an element ofRIbeta mRNA levels increased a median of 2-fold after the last challenge relative to before challenge (P = .007, n = 9). IL-13 protein was detected in supernatants of 7 of 9 subjects' basophil-enriched cultures after the last challenge compared with 3 of 9 basophil-enriched cultures before challenge (median, 6.2 vs 0 pg/mL; P = .058). IL-4 was not detected in any culture supernatant.Conclusion: Intranasal allergen challenge transiently activates circulating basophils by increasing expression of the Fcis an element ofRIbeta subunit and spontaneous IL-13 secretion. Because Fcis an element ofRIbeta is an amplifier of Fcis an element ofRI-mediated responses and IL-13 is proinflammatory, these findings support a primed basophil functional state and demonstrate a systemic effect of local allergen challenge that could contribute in exacerbating allergic reactions.