Saini Sarbjit, Bloom D Candy, Bieneman Anja, Vasagar Kavitha, Togias Alkis, Schroeder John
Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 2004 Oct;114(4):768-74. doi: 10.1016/j.jaci.2004.06.015.
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.
We investigated whether local intranasal allergen challenge alters the phenotype of circulating basophils to a primed state.
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 FcepsilonRIbeta protein by means of Western blotting and for FcepsilonRIbeta mRNA expression by means of real-time PCR. Basophils were also compared with regard to spontaneous secretion of IL-4 and IL-13.
Basophil FcepsilonRIbeta protein levels increased in 5 of 6 subjects after allergen challenge relative to before challenge. Likewise, basophil FcepsilonRIbeta 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.
Intranasal allergen challenge transiently activates circulating basophils by increasing expression of the FcepsilonRIbeta subunit and spontaneous IL-13 secretion. Because FcepsilonRIbeta is an amplifier of FcepsilonRI-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.
气道过敏原激发试验表明,局部气道组织中细胞因子上调,对嗜酸性粒细胞和嗜碱性粒细胞的骨髓前体细胞有远端效应。
我们研究了局部鼻内过敏原激发是否会将循环嗜碱性粒细胞的表型改变为致敏状态。
10名变应性鼻炎患者连续3天通过鼻内喷雾给予过敏原激发。在激发前以及第三次过敏原激发后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激发前和最后一次过敏原激发后嗜碱性粒细胞的FcepsilonRIβ蛋白水平,并通过实时PCR比较FcepsilonRIβ mRNA表达。还比较了嗜碱性粒细胞的IL-4和IL-13自发分泌情况。
与激发前相比,6名受试者中有5名在过敏原激发后嗜碱性粒细胞FcepsilonRIβ蛋白水平升高。同样,与激发前相比,最后一次激发后嗜碱性粒细胞FcepsilonRIβ mRNA水平中位数增加了2倍(P = 0.007,n = 9)。与激发前9份嗜碱性粒细胞富集培养物中的3份相比,最后一次激发后9份嗜碱性粒细胞富集培养物中的7份培养上清液中检测到IL-13蛋白(中位数,6.2对0 pg/mL;P = 0.058)。在任何培养上清液中均未检测到IL-4。
鼻内过敏原激发通过增加FcepsilonRIβ亚基的表达和自发IL-13分泌来短暂激活循环嗜碱性粒细胞。由于FcepsilonRIβ是FcepsilonRI介导反应的放大器,且IL-13具有促炎作用,这些发现支持了嗜碱性粒细胞的致敏功能状态,并证明了局部过敏原激发的全身效应可能导致过敏反应加剧。