CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation

CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation
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DOI:
10.1016/j.jaci.2008.10.022
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发表时间:
2009-02-01
影响因子:
14.2
通讯作者:
Delespesse, Guy
Delespesse, Guy
中科院分区:
医学1区
文献类型:
--
作者:
Allakhverdi, Zoulfia;Comeau, Michael R.;Delespesse, Guy

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背景:在稳态下,造血祖细胞不断从骨髓(BM)进入血液,并在外周组织中循环。在过敏性疾病中,骨髓释放出更多的CD34(+)祖细胞,它们迁移到过敏性炎症部位,在那里分化为组织驻留细胞以及经典的过敏性效应细胞,如肥大细胞、嗜酸性粒细胞和嗜碱性粒细胞。 目的:检验外周血CD34(+)细胞除了作为祖细胞外,是否还能直接作为炎症效应细胞发挥作用。 方法:对高度纯化的新生儿或成人血液CD34(+)细胞进行检查,以确定其胸腺基质淋巴细胞生成素(TSLP)和白细胞介素 - 33(IL - 33)受体的表达情况,以及它们对这些细胞因子以及来自鼻窦炎患者和对照受试者的原代小气道上皮细胞和鼻黏膜外植体上清液的反应。对哮喘患者在吸入过敏原前后的痰液进行检查,以确定是否存在含白细胞介素 - 5(IL - 5)和白细胞介素 - 13(IL - 13)的CD34(+)细胞。 结果:循环中的CD34(+)细胞表达TSLP和IL - 33受体,并通过快速释放高水平的促炎性T(H)2样细胞因子和趋化因子对这些细胞因子作出反应。这些细胞被激活的原代人小气道上皮细胞和慢性鼻窦炎患者鼻黏膜外植体的上清液以TSLP依赖的方式激活。此外,在过敏性哮喘患者的痰液中可以检测到含有IL - 5和IL - 13的活化CD34(+)细胞,并且在特异性过敏原吸入激发后其数量增加。 结论:血液CD34(+)细胞除了作为祖细胞外,自身还可作为促炎性效应细胞,直接促进过敏性炎症。(《过敏与临床免疫学杂志》2009年;123卷:472 - 48页)
Background: In steady state, hemopoietic progenitors constantly egress from the bone marrow (BM) into the blood and circulate through the peripheral tissues. In allergic diseases, the BM releases increased numbers of CD34(+) progenitor cells that migrate to the site of allergic inflammation, where they differentiate into tissue-dwelling and classic effector cells of allergy, such as mast cells, eosinophils, and basophils.Objective: To examine whether peripheral blood CD34(+) cells in addition to being progenitors may also directly function as inflammatory effector cells. Methods: Highly purified neonatal or adult blood CD34(+) cells were examined for the expression of thymic stromal lymphopoietin (TSLP) and IL-33 receptors and for their response to these cytokines as well as to supernatants of primary small airway epithelial cells and nasal explants from rhinosinusitis and control subjects. Sputum of patients with asthma was examined before and after allergen inhalation for the presence of IL-5 and IL-13-containing CD34(+) cells.Results: Circulating CD34(+) cells expressed receptors for TSLP and IL-33 and responded to these cytokines by rapidly releasing high levels of proinflammatory T(H)2-like cytokines and chemokines. These cells were activated in a TSLP-dependent manner by the supernatant fluids from activated primary human small airway epithelial cells and from nasal explants of patients with chronic rhinosinusitis. Moreover, activated CD34(+) cells containing IL-5 and IL-13 could be detected in the sputum of individuals with allergic asthma, with numbers increasing in response to specific allergen inhalation challenge.Conclusion: Blood CD34(+) cells, in addition to being progenitors, may act as proinflammatory effector cells by themselves and directly contribute to the allergic inflammation. (J Allergy Clin Immunol 2009;123:472-8.)