Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen.
Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen.
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DOI：
10.4049/jimmunol.1700055
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Bieneman AP
中科院分区：
文献类型：
--
作者：
Schroeder JT;Bieneman AP
上皮细胞（EC）衍生的细胞因子（如TSLP）激活人类嗜碱性粒细胞的证据仍然存在争议。因此，我们假设内皮细胞可以通过细胞间相互作用直接激活嗜碱性粒细胞。将培养基中的嗜碱性粒细胞单独或与IL-3±抗IgE一起与TSLP、IL-33或IL-25共孵育。类似实验将嗜碱性粒细胞直接与EC系共培养（1- 72小时）。测试上清液的介质和细胞因子。测试靶向受体的抗体的中和作用。乳酸（pH 3.9）处理结合被动致敏测试IgE的作用。总的来说，IL-33增加了IL-13从与IL-3共处理的嗜碱性粒细胞的分泌，对组胺和IL-4的影响最小。相反，当与A549 EC和IL-3共培养时，嗜碱性粒细胞（而不是肥大细胞）释放组胺和显著水平的IL-4/IL-13（10倍），而没有外源性过敏原或IgE交联刺激。不能检测IL-33/TSLP，或中和它们的活性，提示A549 EC激活嗜碱性粒细胞的独特模式。组胺（4小时）和IL-4（5小时）分泌的半最大速率比标准IgE依赖性激活观察到的慢。免疫球蛋白剥离结合被动致敏±奥马珠单抗显示对嗜碱性粒细胞结合IgE的依赖性，通过细胞间接触、聚集和Fcε RI依赖性信号传导的要求得到证实。在发现N-乙酰乳糖胺抑制共培养物中嗜碱性粒细胞活化后，涉及与A549 EC相关的尚未鉴定的IgE结合凝集素。这些发现表明嗜碱性粒细胞的凝集素依赖性激活需要IgE，但不依赖于过敏原或分泌的细胞因子。在进一步研究之前，我们预测这种独特的激活模式与炎症条件有关，尽管没有任何已知的过敏原，但嗜碱性粒细胞的IgE依赖性激活仍会发生。
Evidence for epithelial cell (EC)-derived cytokines (e.g. TSLP) activating human basophils remains controversial. We therefore hypothesize that ECs can directly activate basophils via cell-to-cell interaction. Basophils in medium alone or with IL-3±anti-IgE, were co-incubated with TSLP, IL-33, or IL-25. Analogous experiments co-cultured basophils (1–72h) directly with EC lines. Supernatants were tested for mediators and cytokines. Antibodies targeting receptors were tested for neutralizing effects. Lactic acid (pH 3.9) treatment combined with passive sensitization tested the role of IgE. Overall, IL-33 augmented IL-13 secretion from basophils co-treated with IL-3, with minimal effects on histamine and IL-4. Conversely, basophils (but not mast cells) released histamine and marked levels of IL-4/IL-13 (10-fold) when co-cultured with A549 EC and IL-3, without exogenous allergen or IgE cross-linking stimuli. The inability to detect IL-33/TSLP, or to neutralize their activity, suggested a unique mode of basophil activation by A549 EC. Half-maximal rates for histamine (4h) and IL-4 (5h) secretion were slower than observed with standard IgE-dependent activation. Immunoglobulin stripping combined with passive sensitization±omalizumab showed a dependency for basophil-bound IgE, substantiated by requirement for cell-to-cell contact, aggregation, and FcεRI-dependent signaling. A yet unidentified IgE-binding lectin associated with A549 EC is implicated after discovering that n-acetyllactosamine suppressed basophil activation in co-cultures. These findings point to a lectin-dependent activation of basophil requiring IgE but independent of allergen or secreted cytokine. Pending further investigation, we predict this unique mode of activation is linked to inflammatory conditions whereby IgE-dependent activation of basophils occurs despite absence of any known allergen.
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影响因子：
3.8
作者：
Castillo, Eliseo F.;Schluns, Kimberly S.
通讯作者：
Schluns, Kimberly S.
DOI：
10.1084/jem.20062211
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allakhverdi Z;Comeau MR;Jessup HK;Yoon BR;Brewer A;Chartier S;Paquette N;Ziegler SF;Sarfati M;Delespesse G
通讯作者：
Delespesse G
影响因子：
4.6
作者：
Larsen L;Chen HY;Saegusa J;Liu FT
通讯作者：
Liu FT
影响因子：
11.2
作者：
De Monte, Lucia;Wormann, Sonja;Protti, Maria Pia
通讯作者：
Protti, Maria Pia
影响因子：
4.4
作者：
MacGlashan, Donald, Jr.;Vilarino, Natalia
通讯作者：
Vilarino, Natalia