Fernandes Rochelle, Kusel Merci, Cyr Michael, Sehmi Roma, Holt Kathryn, Holt Barbara, Kebadze Tatiana, Johnston Sebastian L, Sly Peter, Denburg Judah A, Holt Patrick
Division of Allergy and Clinical Immunology, McMaster University, Hamilton, ON, Canada.
Pediatr Allergy Immunol. 2008 May;19(3):239-47. doi: 10.1111/j.1399-3038.2007.00615.x.
Atopy is characterized by eosinophilic inflammation associated with recruitment of eosinophil/basophil (Eo/B) progenitors. We have previously shown that Eo/B progenitor phenotypes are altered in cord blood (CB) in infants at high risk of atopy/asthma, and respond to maternal dietary intervention during pregnancy. As respiratory tract viral infections have been shown to induce wheeze in infancy, we investigated the relationship between CB progenitor function and phenotype and acute respiratory illness (ARI), specifically wheeze and fever. CB from 39 high-risk infants was studied by flow cytometry for CD34(+) progenitor phenotype and by ex vivo Eo/B-colony forming unit (CFU) responses to cytokine stimulation in relation to ARI in the first year of life. A consistent relationship was observed between increased numbers of granulocyte/macrophage (GM)-colony-stimulating factor (CSF)- and IL-3-responsive Eo/B-CFU in CB and the frequency/characteristics of ARI during infancy. Comparable associations were found between ARI and CB IL-3R(+) and GM-CSFR(+)CD34(+) cell numbers. Conversely, a reciprocal decrease in the proportion of CB IL-5R(+) cells was found in relation to the clinical outcomes. The elevation of IL-3/GM-CSF-responsive Eo/B progenitors in high-risk infants in relation to ARI outcomes suggests a mechanism for the increased severity of inflammatory responses in these subjects following viral infection.
特应性的特征是与嗜酸性粒细胞/嗜碱性粒细胞(Eo/B)祖细胞募集相关的嗜酸性粒细胞炎症。我们之前已经表明,在有特应性/哮喘高风险的婴儿的脐带血(CB)中,Eo/B祖细胞表型发生改变,并且在孕期对母亲的饮食干预有反应。由于呼吸道病毒感染已被证明会在婴儿期诱发喘息,我们研究了CB祖细胞功能和表型与急性呼吸道疾病(ARI)之间的关系,特别是喘息和发热。通过流式细胞术研究了39名高风险婴儿的CB的CD34(+)祖细胞表型,并通过体外Eo/B集落形成单位(CFU)对细胞因子刺激的反应,研究其与生命第一年的ARI的关系。在CB中粒细胞/巨噬细胞(GM)-集落刺激因子(CSF)和IL-3反应性Eo/B-CFU数量增加与婴儿期ARI的频率/特征之间观察到一致的关系。在ARI与CB IL-3R(+)和GM-CSFR(+)CD34(+)细胞数量之间发现了类似的关联。相反,发现CB IL-5R(+)细胞比例与临床结果呈反比下降。高风险婴儿中与ARI结果相关的IL-3/GM-CSF反应性Eo/B祖细胞的升高提示了这些受试者在病毒感染后炎症反应严重程度增加的一种机制。