Allakhverdi Zoulfia, Comeau Michael R, Smith Dirk E, Toy Dean, Endam Leandra Mfuna, Desrosiers Martin, Liu Yong-Jun, Howie Karen J, Denburg Judah A, Gauvreau Gail M, Delespesse Guy
Laboratory on Allergy, Centre Recherche Centre Hospitalier Universite Montreal (CRCHUM), Notre-Dame Hospital, Montreal, Quebec, Canada.
J Allergy Clin Immunol. 2009 Feb;123(2):472-8. doi: 10.1016/j.jaci.2008.10.022. Epub 2008 Dec 6.
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.
To examine whether peripheral blood CD34(+) cells in addition to being progenitors may also directly function as inflammatory effector cells.
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.
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.
Blood CD34(+) cells, in addition to being progenitors, may act as proinflammatory effector cells by themselves and directly contribute to the allergic inflammation.
在稳态下，造血祖细胞持续从骨髓（BM）进入血液并循环通过外周组织。在过敏性疾病中，骨髓释放出数量增加的CD34(+)祖细胞，这些细胞迁移至过敏性炎症部位，在那里它们分化为驻留组织的和经典的过敏效应细胞，如肥大细胞、嗜酸性粒细胞和嗜碱性粒细胞。
研究外周血CD34(+)细胞除作为祖细胞外，是否也可直接作为炎症效应细胞发挥作用。
检测高度纯化的新生儿或成人血液CD34(+)细胞中胸腺基质淋巴细胞生成素（TSLP）和IL-33受体的表达，以及它们对这些细胞因子以及来自原发性小气道上皮细胞和鼻窦炎患者及对照受试者鼻外植体上清液的反应。在变应原吸入前后，检测哮喘患者痰液中含IL-5和IL-13的CD34(+)细胞的存在情况。
循环CD34(+)细胞表达TSLP和IL-33受体，并通过快速释放高水平的促炎T(H)2样细胞因子和趋化因子对这些细胞因子作出反应。这些细胞被活化的原代人小气道上皮细胞和慢性鼻窦炎患者鼻外植体的上清液以TSLP依赖的方式激活。此外，在过敏性哮喘患者的痰液中可检测到含有IL-5和IL-13的活化CD34(+)细胞，其数量在特异性变应原吸入激发后增加。
血液CD34(+)细胞除作为祖细胞外，自身可能作为促炎效应细胞发挥作用，并直接促成过敏性炎症。
