哮喘患儿外周血T淋巴细胞上前列腺素D2受体改变研究

应延风, 胡野, 单小云, 杜娟, 屠平光

中国当代儿科杂志 ›› 2009, Vol. 11 ›› Issue (03) : 199-202.

PDF(1015 KB)
PDF(1015 KB)
中国当代儿科杂志 ›› 2009, Vol. 11 ›› Issue (03) : 199-202.
论著·临床研究

哮喘患儿外周血T淋巴细胞上前列腺素D2受体改变研究

  • 应延风,胡野,单小云,杜娟,屠平光
作者信息 +

Changes of prostaglandin D2 receptor on T cells in peripheral blood of children with asthma

  • YING Yan-Feng, HU Ye, SHAN Xiao-Yun, DU Juan, TU Ping-Guang
Author information +
文章历史 +

摘要

目的:哮喘的慢性气道炎症与TH2的极化有关,炎症介质前列腺素D2(PGD2)可通过T淋巴细胞上前列腺素D2受体(DP1/CRTH2)调控其极化和分泌功能,而且CRTH2是TH2细胞的特征性受体,研究不同哮喘病期T淋巴细胞上受体改变,对了解哮喘患儿中TH2极化状态和哮喘发病机制有重要意义。方法:正常对照组35例,哮喘急性发作期组42例和临床缓解期组30例。用酶联免疫吸附法测定外周血IL-4,IL-5 和IFN-γ,用放射配体结合分析法测定外周血T细胞上DP1/CRTH2结合容量。结果:哮喘急性发作期和临床缓解期组T淋巴细胞上总结合和CRTH2受体结合容量比正常对照组显著增加(P<0.01);DP1差异无显著性。哮喘急性发作期和临床缓解期组TH2细胞因子IL-4、IL-5比正常对照组显著增加(P<0.01);TH1细胞因子IFN-γ比正常对照组显著减少(P<0.01)。结论:支气管哮喘病人临床缓解期和急性发作期外周血T淋巴细胞上CRTH2受体表达增加,外周血中TH2细胞因子分泌增加, TH1细胞因子分泌减少, 提示在哮喘病人中存在TH2的极化状态,应用CRTH2拮抗剂可能是以后哮喘治疗的一个新靶点。[中国当代儿科杂志,2009,11(3):199-202]

Abstract

OBJECTIVE: Chronic airway inflammation is associated with the polarization of TH2 cells in asthma. Prostaglandin D2 (PGD2) plays an important role in the polarization of TH2 cells. This study aimed to investigate the changes of PGD2 receptors (DP1/CRTH2) on T lymphocytes and their significance in asthma. METHODS: Seventy-two children with asthma were assigned to two groups: acute attack (n=42) and remission (n=30). Thirty-five healthy children were used as the control group. Plasma levels of TH2 cytokines IL-4 and IL-5, and TH1 cytokine INF-γ were detected using ELISA. Radiological binding assay (RBA) was used to measure the contents of DP1/CRTH2 receptors on T cells in peripheral blood (PPB). RESULTS: The total combining contents of DP and CRTH2 on T cells in PPB in the acute attack and the remission groups were significantly higher than those in the control group (P<0.01). There was no significant difference in the DP1 content among the three groups. Serum levels of IL-4 and IL-5 significantly increased (P<0.01), in contrast, serum levels of TH1 cytokine IFN-γ were significantly reduced in the acute attack and the remission groups compared with those in the control group (P<0.01). CONCLUSIONS:The total combining contents of DP and CRTH2 on T cells increased, serum levels of TH2 cytokines also increased, but serum levels of TH1 cytokine decreased significantly in the acute attack and the remission phases in children with asthma. This showed that a polarization of TH2 cells occurred in children with asthma and suggested that CRTH2 antagonism may be a new target for the treatment of asthma.[Chin J Contemp Pediatr, 2009, 11 (3):199-202]

关键词

哮喘 / 淋巴细胞 / CRTH2 / 儿童

Key words

Asthma / Lymphocyte / CRTH2 / Child

引用本文

导出引用
应延风, 胡野, 单小云, 杜娟, 屠平光. 哮喘患儿外周血T淋巴细胞上前列腺素D2受体改变研究[J]. 中国当代儿科杂志. 2009, 11(03): 199-202
YING Yan-Feng, HU Ye, SHAN Xiao-Yun, DU Juan, TU Ping-Guang. Changes of prostaglandin D2 receptor on T cells in peripheral blood of children with asthma[J]. Chinese Journal of Contemporary Pediatrics. 2009, 11(03): 199-202
中图分类号: R562.2+5   

参考文献

[1]Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane recepor CRTH2[J]. J Exp Med, 2001, 193(2):255-261.
[2]Nagata K, Tanaka K, Ogawa K, Kenmotsu K, Imai T, Yoshie O, et al. Selective expression of a novel surface molecule by human Th2 cell in vivo[J]. J Immunol, 1999, 162(3):1278-1286.
[3]Iwasaki M, Nagata K, Takano S, Takahashi K, Ishii N, Ikezawa Z, et al. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis [J]. J Invest Dermatol, 2002, 119(3): 609-616.
[4]中华医学会儿科学分会呼吸学组,中华医学会《中华儿科杂志》编辑委员会. 儿童支气管哮喘防治常规(试行)(2003 年修订)[J]. 中华儿科杂志,2004,42(2):100-107.
[5]Virgolini I, Li S, Sillaber C, Majdic O, Sinzinger H, Lechner K, et al. Characterization of prostaglandin (PG)-binding sites expressed on human basophils: Evidence for a prostaglandin E1,I2 and A D2 receptor[J] .J Bio Chemistry, 1992, 267(18):12700-12708.
[6]Uller L, Mathiesen JM, Alenmyr L, Korsgren M, Ulven T, Hogberg T, et al. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation[J]. Respir Res, 2007, 28, 8(1):16-26.
[7]Xue L, Gyles SL, Wettey FR, Gazi L, Townsend E, Hunter MG, et al. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-Like molecule expressed on Th2 cells[J]. J Immunol, 2005, 175(10): 6531-6536.
[8]Hardy CC, Robinson C, Tattersfield AE, Holgate ST. The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic man[J]. N Engl J Med, 1984, 311(4):209-213.
[9]O′Sullivan S, Roquet A, Dahlén B, Dahlen SE, Kumlin M. Urinary excretion ofinflammatory mediators during allergen-induced early and late phase asthmatic reactions[J]. Clin Exp Allergy, 1998, 28(11):1332-1339.
[10]Murray JJ,Tonnel AB,Brash AR, Roberts LJ 2nd, Gosset P, Workman R, et al.Release of prostaglandin D2 into human airways during acute antigen challenge[J]. N Engl J Med, 1986, 315(13):800-804.
[11]Brightling CE, Ward R, Woltmann G, Bradding P, Sheller JR, Dworski R, et al. Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma[J]. Am J Respir Crit Care Med, 2000, 162(3):878-882.
[12]Abe H, Takeshita T, Nagata K, Arita T, Endo Y, Fujita T, et al. Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family[J]. Gene, 1999, 227(1):71-77.
[13]De Fanis U, Mori F, Kurnat RJ, Lee WK, Bova M, Adkinson NF, et al. GATA3 upregulation associated with surface expression of CD294/CRTH2:a unique feature of human Th cells[J]. Blood, 2007, 109 (10) :4343-4350.
[14]Tsuda H, Michimata T, Sakai M, Nagata K, Nakamura M, Saito S. A novel surface molecule of TH2-andTc2-type cells, CRTH2 expression on human peripheral and de-cidual CD4+and CD8+T cells during the early stage of pregnancy[J]. Clin Exp Immunol, 2001, 123(1):105-111.
[15]Karagiannidis C, Hense G, Rueckert B, Mantel PY, Ichters B, Blaser K, et al. High-altitude climate therapy reduces local airway inflammation and modulates lymphocyte activation[J]. Scand J Immunol, 2006, 63(4):304-310.
[16]Takeshita K, Yamasaki T Nagao K, Sugimoto H, Shichijo M, Gantner F, et al. CRTH2 is a prominent effector in contact hypersensitivityinduced neutrophil inflammation[J].Int immunol, 2004, 16(7):947-959.
[17]肖春香,殷小成,尹珊辉,匡艳华,王金兰. 哮喘患儿血清IL-18、IL-4和INF-γ水平测定的临床意义的研究[J].实用诊断与治疗杂志, 2006, 20(4):240-241.
[18]董蔚,盛军,浦燕艳,石学耕,史桂英.哮喘患儿红细胞内IL-4,INF-γ和血清IgE测定及临床意义[J].中国当代儿科杂志,2002,4(2):119-120.
[19]何学华,李云,杨于嘉,易红玲.灭活卡介苗经皮接种治疗婴幼儿哮喘对IgE,ECP,INF-γ, IL-4水平的影响[J].中国当代儿科杂志,2004,6(3):191-194.
[20]Oguma T, Palmer LJ, Birben E, Sonna LA, Asano K, Lilly CM. Role of prostanoid DP receptor variants in susceptibility to asthma[J]. N Engl J Med, 2004, 351(17):1752-1763.
[21]Huang JL, Gao PS, Mathias RA, Yao TC, Chen LC, Kuo ML, et al. Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability[J]. Hum Mol Genet, 2004, 13(21):2691-12697.


PDF(1015 KB)

Accesses

Citation

Detail

段落导航
相关文章

/