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人 CD34 细胞体外表达和释放白细胞介素 5;哮喘和变应性肉芽肿性血管炎病例的体外证据。

IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.

机构信息

Krefting Research Centre, Department of Internal Medicine, Institute of Medicine, Göteborg University, Sweden.

出版信息

Allergy. 2010 Jul;65(7):831-9. doi: 10.1111/j.1398-9995.2009.02271.x. Epub 2009 Nov 26.

Abstract

BACKGROUND

Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease.

METHODS

CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed.

RESULTS

Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma.

CONCLUSION

CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.

摘要

背景

嗜酸性粒细胞在白细胞介素-5(IL-5)的影响下,从骨髓(BM)中的造血 CD34(+)祖细胞中发育而来。IL-5 的主要来源是 T 淋巴细胞,但也可能存在其他来源。本研究的目的是确定人外周血(PB)和 BM 中的 CD34(+)细胞在体外刺激时是否具有产生 IL-5 的能力,其次是确定在进行性嗜酸性粒细胞疾病中是否可以在原位找到产生 IL-5 的 CD34(+)细胞数量增加。

方法

体外刺激 PB 和 BM 的 CD34(+)细胞,并通过 ELISA、ELISPOT、流式细胞术和免疫细胞化学评估 IL-5 的产生和释放。通过流式细胞术分析 Churg-Strauss 综合征患者的血液和 BM 中的 CD34(+)/IL-5(+)细胞,并对哮喘患者支气管活检组织中的 CD34(+)/IL-5(+)细胞进行免疫组织化学染色。

结果

PB 和 BM 的 CD34(+)细胞在体外刺激时均可产生和释放 IL-5。在 Churg-Strauss 患者中,在 PB 和 BM 中发现了产生 IL-5 的 CD34(+)细胞。口服糖皮质激素治疗可显著减少 BM 中 IL-5 阳性 CD34 细胞的数量。哮喘患者存在 CD34(+)/IL-5(+)细胞。

结论

血液和 BM 中的 CD34(+)细胞既能在体外又能在体内产生和释放 IL-5,这表明这些细胞可能有能力有助于嗜酸性粒细胞炎症。因此,靶向产生和释放 IL-5 的 CD34(+)祖细胞可能有助于减少嗜酸性粒细胞驱动疾病中嗜酸性粒细胞谱系定向细胞的动员。

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