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肺部趋化因子及其受体可区分患哮喘和慢性咳嗽的儿童。

Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough.

作者信息

Hartl Dominik, Griese Matthias, Nicolai Thomas, Zissel Gernot, Prell Christine, Konstantopoulos Nikolaos, Gruber Rudolf, Reinhardt Dietrich, Schendel Dolores J, Krauss-Etschmann Susanne

机构信息

Children's Hospital of the Ludwig-Maximilians-University of Munich, Lindwurmstrasse 2a, D-80337 Munich, Germany.

出版信息

J Allergy Clin Immunol. 2005 Apr;115(4):728-36. doi: 10.1016/j.jaci.2004.11.049.

Abstract

BACKGROUND

Cough is a frequent symptom in children, but the differentiation of asthmatic cough from cough of other origins can be difficult. Chemokines recruit T lymphocytes to inflamed tissues, and the corresponding chemokine receptors are differentially expressed on T H 1 and T H 2 cells.

OBJECTIVE

We sought to determine whether levels of T H 1/T H 2-related chemokines and their receptors differ in bronchoalveolar lavage fluid (BALF) from 12 children with allergic asthma, 15 nonatopic children with chronic cough, and 10 children without airway disease.

METHODS

The T H 1-related (IFN-gamma-inducible protein of 10 kd [IP-10], IFN-gamma-inducible T cell alpha chemoattractant [ITAC], monokine induced by IFN-gamma [Mig], and IFN-gamma) and T H 2-related (thymus- and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC], IL-5, and IL-4) chemokines and cytokines were quantified in BALF by ELISA and a particle-based multiplex array. Percentages of pulmonary lymphocytes expressing CXCR3 + and CCR5 + (T H 1) and CCR4 + and CCR3 + (T H 2) chemokine receptors were determined in BALF by flow cytometry.

RESULTS

Pulmonary CCR4 + CD4 + cells and levels of TARC and MDC were significantly increased in asthmatic children versus children with chronic cough or without airway disease. In asthmatic children CCR4 + CD4 + cells correlated positively with levels of TARC, MDC, and serum IgE levels and negatively with FEV 1 . In contrast, CXCR3 + CD8 + cells and levels of ITAC were significantly increased in children with non-atopic chronic cough compared with the other groups. In children with chronic cough, CXCR3 + CD8 + cells correlated with levels of ITAC and IFN-gamma.

CONCLUSION

Pulmonary CCR4 + CD4 + and CXCR3 + CD8 + cells and their ligands TARC, MDC, and ITAC clearly differentiate asthmatic children from nonatopic children with chronic cough. The analysis of these markers could facilitate the diagnostic discrimination of asthma versus other reasons for chronic cough in children.

摘要

背景

咳嗽是儿童常见症状,但区分哮喘性咳嗽与其他原因引起的咳嗽可能存在困难。趋化因子可将T淋巴细胞募集到炎症组织,相应的趋化因子受体在TH1和TH2细胞上呈差异表达。

目的

我们试图确定12例过敏性哮喘儿童、15例非特应性慢性咳嗽儿童和10例无气道疾病儿童的支气管肺泡灌洗液(BALF)中TH1/TH2相关趋化因子及其受体水平是否存在差异。

方法

采用酶联免疫吸附测定(ELISA)和基于微粒的多重分析方法,对BALF中TH1相关(10kd的γ干扰素诱导蛋白[IP-10]、γ干扰素诱导T细胞α趋化因子[ITAC]、γ干扰素诱导的单核因子[Mig]和γ干扰素)及TH2相关(胸腺和活化调节趋化因子[TARC]、巨噬细胞衍生趋化因子[MDC]、白细胞介素-5和白细胞介素-4)趋化因子和细胞因子进行定量分析。采用流式细胞术测定BALF中表达CXCR3+和CCR5+(TH1)以及CCR4+和CCR3+(TH2)趋化因子受体的肺淋巴细胞百分比。

结果

与慢性咳嗽儿童或无气道疾病儿童相比,哮喘儿童的肺CCR4+CD4+细胞以及TARC和MDC水平显著升高。在哮喘儿童中,CCR4+CD4+细胞与TARC、MDC水平及血清IgE水平呈正相关,与第一秒用力呼气容积(FEV1)呈负相关。相反,与其他组相比,非特应性慢性咳嗽儿童的CXCR3+CD8+细胞及ITAC水平显著升高。在慢性咳嗽儿童中,CXCR3+CD8+细胞与ITAC及γ干扰素水平相关。

结论

肺CCR4+CD4+和CXCR3+CD8+细胞及其配体TARC、MDC和ITAC可明确区分哮喘儿童与非特应性慢性咳嗽儿童。对这些标志物的分析有助于儿童哮喘与其他慢性咳嗽原因的诊断鉴别。

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