表达白细胞介素-5受体信使核糖核酸的骨髓源性CD34 +细胞与哮喘气道炎症之间的关系。

Relationship between bone marrow-derived CD34 + cells expressing interleukin-5 receptor messenger RNA and asthmatic airway inflammation.

作者信息

Mao Hui, Wang Zeng-li, Li Fu-yu, Liu Chun-tao, Lei Song

机构信息

Respiratory Department, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029.

出版信息

Chin Med J (Engl). 2004 Jan;117(1):24-9.

PMID:14733768

Abstract

BACKGROUND

Asthma is clinically related with the degree of eosinophilic inflammation. How asthmatic airway inflammation is affected is still poorly understood. So the effects of bone marrow-derived hematopoietic cells expressing CD(34) (CD(34)(+)) and interleukin-5 (IL-5) receptor messenger RNA (IL-5R mRNA+) on asthmatic airway inflammation were investigated.

METHODS

Balb/c mice were sensitized and challenged by ovalbumin (OVA) to establish an asthmatic model while control mice were sensitized and exposed to sterile saline. The mice were killed at different time points after being challenged by OVA and sterile saline. Then, bronchoalveolar lavage fluid (BALF), peripheral blood (PB) and bone marrow (BM) were prepared. Eosinophils in PB (PBEOS) and BALF (BALFEOS), nuclear cells in BALF, PB and BM were counted. By flow cytometry, the percentage of CD(34)(+) cells to nucleated cells in PB, BM and the relative number of CD(34)(+) cells in PB (PBCD(34)(+)) and BM (BMCD(34)(+)) were calculated. Immunocytochemistry and in situ hybridization were used to investigate the hematopoietic cells with co-localized expression of CD(34) and IL-5R mRNA in BM (BMCD34+IL-5R mRNA+). The percentage of BMCD34+IL-5R mRNA+ to BMCD(34)(+) was calculated.

RESULTS

Twelve hours after challenge by OVA, BALFEOS and PBEOS in the experimental group were significantly higher than those in the control group (P < 0.01). Twenty-four hours after OVA challenge, BALFEOS, PBEOS and BMCD34+IL-5R mRNA+ were elevated maximally, significantly different from those in the control group (P < 0.01). Forty-eight hours after OVA challenge, BALFEOS and BMCD34+IL-5R mRNA+ were still significantly higher than those of the controls (P < 0.01). The other markers reverted to normal. In 60 mice, BMCD34+IL-5R mRNA+ was closely correlated with the BALEOS, PBEOS, BMCD(34)(+) and BMCD(34)(+) (%) (P < 0.05).

CONCLUSIONS

The amount of CD(34)(+) cells expressing IL-5R mRNA increased in the BM of asthmatic model mice, which favors eosinophilopoiesis and eosinophilic airway inflammation. A signal pathway exists between the lungs and the bone marrow, which is involved in the initiation and maintenance of asthmatic airway inflammation.

摘要

背景

哮喘在临床上与嗜酸性粒细胞炎症程度相关。哮喘气道炎症如何受到影响仍知之甚少。因此，研究了表达CD(34)（CD(34)(+)）和白细胞介素-5（IL-5）受体信使核糖核酸（IL-5R mRNA+）的骨髓造血细胞对哮喘气道炎症的影响。

方法

用卵清蛋白（OVA）对Balb/c小鼠进行致敏和激发以建立哮喘模型，而对照小鼠则用无菌盐水进行致敏和暴露。在OVA和无菌盐水激发后不同时间点处死小鼠。然后，制备支气管肺泡灌洗液（BALF）、外周血（PB）和骨髓（BM）。对PB中的嗜酸性粒细胞（PBEOS）和BALF中的嗜酸性粒细胞（BALFEOS）、BALF、PB和BM中的核细胞进行计数。通过流式细胞术，计算PB、BM中CD(34)(+)细胞占核细胞的百分比以及PB（PBCD(34)(+)）和BM（BMCD(34)(+)）中CD(34)(+)细胞的相对数量。采用免疫细胞化学和原位杂交技术研究BM中CD(34)和IL-5R mRNA共定位表达的造血细胞（BMCD34+IL-5R mRNA+）。计算BMCD34+IL-5R mRNA+占BMCD(34)(+)的百分比。

结果

OVA激发12小时后，实验组的BALFEOS和PBEOS显著高于对照组（P<0.01）。OVA激发24小时后，BALFEOS、PBEOS和BMCD34+IL-5R mRNA+达到最高水平，与对照组相比有显著差异（P<0.01）。OVA激发48小时后，BALFEOS和BMCD34+IL-5R mRNA+仍显著高于对照组（P<0.01）。其他指标恢复正常。在60只小鼠中，BMCD34+IL-5R mRNA+与BALEOS、PBEOS、BMCD(34)(+)和BMCD(34)(+)（%）密切相关（P<0.05）。