Please wait a minute...
Journal of ZheJiang University(Medical Science)  2016, Vol. 45 Issue (5): 544-549    DOI: 10.3785/j.issn.1008-9292.2016.09.15
    
Reasearch progress on the role of neutrophils in asthma
LI Tingting, KE Yuehai, CHENG Hongqiang
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China
Download: HTML (   PDF(615KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Asthma is a phenotypically heterogeneous chronic disease of the airways. Studies have found that neutrophils are crucial to airway inflammation in acute asthma, persistent asthma, particularly in asthma of poor response to glucocorticoid treatment. The role of neutrophils in development of bronchial asthma is complex, as they can release a potent source of cytokines and inflammatory mediators participating in asthma. Differing from eosinophilic inflammatory asthma, neutrophilic inflammatory asthma is not depend on helper T (Th)2 cells, but may be related to Th1 and Th17 cells. This review highlights the role of neutrophils in the development of asthma, and the treatment of neutrophilic asthma with biological agents and novel small molecules.



Key wordsAsthma/physiopathology      Neutrophils/physiology      Helper T cell      Review     
Received: 25 June 2016      Published: 25 September 2016
CLC:  R562  
  R363  
Cite this article:

LI Tingting, KE Yuehai, CHENG Hongqiang. Reasearch progress on the role of neutrophils in asthma. Journal of ZheJiang University(Medical Science), 2016, 45(5): 544-549.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2016.09.15     OR     http://www.zjujournals.com/med/Y2016/V45/I5/544


中性粒细胞在哮喘中作用的研究进展

哮喘是一种常见的具有异质性的慢性呼吸道疾病。近年来研究发现,在急性哮喘、持续性哮喘特别是一些糖皮质激素治疗无效的哮喘亚型中,中性粒细胞引起的气道炎症起主导作用。中性粒细胞在哮喘中的作用比较复杂,它可以通过释放一系列的细胞因子及炎症介质参与哮喘的病理过程。大量证据表明,中性粒细胞气道炎症是由辅助性T细胞(Th)17细胞和Th1细胞所调控,而不依赖于Th2细胞。现就中性粒细胞在哮喘中的作用,以及针对中性粒细胞性哮喘在新型小分子药物和生物制剂领域的治疗方法的研究进展加以综述。


关键词: 哮喘/病理生理学,  中性白细胞/生理学,  辅助性T细胞,  综述 
[[1]]   ZEKI A A.Statins and asthma:where we stand, and the next critical steps in research[J].Curr Med Res Opin, 2014, 30(6):1051-1054.
[[2]]   SACKMANN E K, BERTHIER E, SCHWANTES E A, et al.Characterizing asthma from a drop of blood using neutrophil chemotaxis[J].Proc Natl Acad Sci U S A, 2014, 111(16):5813-5818.
[[3]]   THOMSON N C.Novel approaches to the management of noneosinophilic asthma[J].Ther Adv Respir Dis, 2016, 10(3):211-234.
[[4]]   LIM H F, NAIR P.Efficacy and safety of reslizumab in patients with moderate to severe eosinophilic asthma[J].Expert Rev Respir Med, 2015, 9(2):135-142.
[[5]]   NAIR P, AZIZ-UR-REHMAN A, RADFORD K.Therapeutic implications of ‘neutrophilic asthma’[J].Curr Opin Pulm Med, 2015, 21(1):33-38.
[[6]]   GREEN R H, BRIGHTLING C E, BRADDING P.The reclassification of asthma based on subphenotypes[J].Curr Opin Allergy Clin Immunol, 2007, 7(1):43-50.
[[7]]   BRUIJNZEEL P L, UDDIN M, KOENDERMAN L.Targeting neutrophilic inflammation in severe neutrophilic asthma:can we target the disease-relevant neutrophil phenotype?[J].J Leukoc Biol, 2015, 98(4):549-556.
[[8]]   CHOI J S, JANG A S, PARK J S, et al.Role of neutrophils in persistent airway obstruction due to refractory asthma[J].Respirology, 2012, 17(2):322-329.
[[9]]   AMULIC B, CAZALET C, HAYES G L, et al.Neutrophil function:from mechanisms to disease[J].Annu Rev Immunol, 2012, 30:459-489.
[[10]]   HOSOKI K, YING S, CORRIGAN C, et al.Analysis of a panel of 48 cytokines in BAL fluids specifically identifies IL-8 levels as the only cytokine that distinguishes controlled asthma from uncontrolled asthma, and correlates inversely with FEV1[J/OL].PLoS One, 2015, 10(5):e126035.
[[11]]   WENZEL S E, SZEFLER S J, LEUNG D Y, et al.Bronchoscopic evaluation of severe asthma[J].Am J Respir Crit Care Med, 1997, 156(3):1871-1875.
[[12]]   NAKAGOME K, MATSUSHITA S, NAGATA M.Neutrophilic inflammation in severe asthma[J].Int Arch Allergy Immunol, 2012, 158(Suppl 1):96-102.
[[13]]   UDDIN M, NONG G, WARD J, et al.Prosurvival activity for airway neutrophils in severe asthma[J].Thorax, 2010, 65(8):684-689.
[[14]]   CIEPIELA O, OSTAFIN M, DEMKOW U.Neutrophils in asthma-a review[J].Respir Physiol Neurobiol, 2015, 209:13-16.
[[15]]   VAUGHAN K R, STOKES L, PRINCE L R, et al.Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor1[J].J Immunol, 2007, 179(12):8544-8553.
[[16]]   康翼鹏, 周颖, 薛小燕, 等.巨噬细胞吞噬中性粒细胞的协同抗炎作用[J].生理科学进展, 2012, 43(6):455-458.KANG Yipeng, ZHOU Ying, XUE Xiaoyan, et al.Anti-inflammation function of macrophages engulfing neutrophils[J].Progress Physiological Science, 2012, 43(6):455-458.(in Chinese)
[[17]]   SIMPSON J L, GIBSON P G, YANG I A, et al.Impaired macrophage phagocytosis in non-eosinophilic asthma[J].Clin Exp Allergy, 2013, 43(1):29-35.
[[18]]   王新新, 薄建萍.中性粒细胞性哮喘的危险因素研究进展[J].中华哮喘杂志:电子版, 2012, 6(4):270-273.WANG Xinxin, BO Jianping.Progression on the causes of neutrophilic asthma[J].Chinese Journal of Asthma (Electronic Edition), 2012, 6(4):270-273.(in Chinese)
[[19]]   KOLACZKOWSKA E, KUBES P.Neutrophil recruitment and function in health and inflammation[J].Nat Rev Immunol, 2013, 13(3):159-175.
[[20]]   LAVINSKIENE S, BAJORIUNIENE I, MALAKAUSKAS K, et al.Sputum neutrophil count after bronchial allergen challenge is related to peripheral blood neutrophil chemotaxis in asthma patients[J].Inflamm Res, 2014, 63(11):951-959.
[[21]]   MANDA-HANDZLIK A, DEMKOW U.Neutrophils:the role of oxidative and nitrosative stress in health and disease[J].Adv Exp Med Biol, 2015, 857:51-60.
[[22]]   DI STEFANO A, GNEMMI I, VICARI C, et al.Oxidant-antioxidant balance in asthma and the potential of antioxidant therapies[J].Monaldi Arch Chest Dis, 2010, 73(3):96-98.
[[23]]   TECCHIO C, SCAPINI P, PIZZOLO G, et al.On the cytokines produced by human neutrophils in tumors[J].Semin Cancer Biol, 2013, 23(3):159-170.
[[24]]   SUN Q, LIU L, ROTH M, et al.PRMT1 upregulated by epithelial proinflammatory cytokines participates in COX2 expression in fibroblasts and chronic antigen-induced pulmonary inflammation[J].J Immunol, 2015, 195(1):298-306.
[[25]]   SIMPSON J L, BAINES K J, BOYLE M J, et al.Oncostatin M (OSM) is increased in asthma with incompletely reversible airflow obstruction.[J].Exp Lung Res, 2009, 35(9):781-794.
[[26]]   LE BEL M, BRUNET A, GOSSELIN J.Leukotriene B4, an endogenous stimulator of the innate immune response against pathogens[J].J Innate Immun, 2014, 6(2):159-168.
[[27]]   MONTESEIRÍN J.Neutrophils and Asthma[J].J Investig Allergol Clin Immunol, 2009, 19(5):340-354.
[[28]]   LAMBRECHT B N, HAMMAD H.The immunology of asthma[J].Nat Immunol, 2015, 16(1):45-56.
[[29]]   PELAIA G, VATRELLA A, BUSCETI M T, et al.Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma[J].Mediators Inflamm, 2015, 2015:1-8.
[[30]]   HALWANI R, AL-MUHSEN S, HAMID Q.T helper 17 cells in airway diseases:from laboratory bench to bedside[J].Chest, 2013, 143(2):494-501.
[[31]]   LINDÉN A, DAHLÉN B.Interleukin-17 cytokine signalling in patients with asthma[J].Eur Respir J, 2014, 44(5):1319-1331.
[[32]]   SIMPSON J L, PHIPPS S, BAINES K J, et al.Elevated expression of the NLRP3 inflammasome in neutrophilic asthma[J].Eur Respir J, 2014, 43(4):1067-1076.
[[33]]   BRUSSELLE G G, PROVOOST S, BRACKE K R, et al.Inflammasomes in respiratory disease[J].Chest, 2014, 145(5):1121-1133.
[[34]]   LEE T H, SONG H J, PARK C S.Role of inflammasome activation in development and exacerbation of asthma[J].Asia Pacific Allergy, 2014, 4(4):187-196.
[[35]]   VROMAN H, VAN DEN BLINK B, KOOL M.Mode of dendritic cell activation:the decisive hand in Th2/Th17 cell differentiation.Implications in asthma severity?[J].Immunobiology, 2015, 220(2):254-261.
[[36]]   GRIFFIN G K, NEWTON G, TARRIO M L, et al.IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation[J].J Immunol, 2012, 188(12):6287-6299.
[[37]]   CAMPBELL L M, MAXWELL P J, WAUGH D J.Rationale and means to target pro-inflammatory interleukin-8(CXCL8) signaling in cancer[J].Pharmaceuticals (Basel), 2013, 6(8):929-959.
[[38]]   LEAKER B R, BARNES P J, O'CONNOR B.Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist[J].Respir Res, 2013, 14:137.
[[39]]   NAIR P, GAGA M, ZERVAS E, et al.Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils:a randomized, placebo-controlled clinical trial[J].Clin Exp Allergy, 2012, 42(7):1097-1103.
[[40]]   JURCEVIC S, HUMFREY C, UDDIN M, et al.The effect of a selective CXCR2 antagonist (AZD5069) on human blood neutrophil count and innate immune functions[J].Br J Clin Pharmacol, 2015, 80(6):1324-1336.
[[41]]   EVANS J F, FERGUSON A D, MOSLEY R T, et al.What's all the FLAP about?:5-lipoxygenase-activating protein inhibitors for inflammatory diseases[J].Trends Pharmacol Sci, 2008, 29(2):72-78.
[[42]]   BAIN G, KING C D, SCHAAB K, et al.Pharmacodynamics, pharmacokinetics and safety of GSK2190915, a novel oral anti-inflammatory 5-lipoxygenase-activating protein inhibitor[J].Br J Clin Pharmacol, 2012, 75(3):779-790.
[[43]]   BUSSE W W, HOLGATE S, KERWIN E, et al.Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma[J].Am J Respir Crit Care Med, 2013, 188(11):1294-1302.
[[44]]   GUPTA A, DIMELOE S, RICHARDS D F, et al.Defective IL-10 expression and in vitro steroid-induced IL-17A in paediatric severe therapy-resistant asthma[J].Thorax, 2014, 69(6):508-515.
[[45]]   WENZEL S E, BARNES P J, BLEECKER E R, et al.A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma[J].Am J Respir Crit Care Med, 2009, 179(7):549-558.
[1] FENG Mengyu,ZHANG Taiping,ZHAO Yupei. Present situation and prospect of enhanced recovery after surgery in pancreatic surgery[J]. Journal of ZheJiang University(Medical Science), 2017, 46(6): 666-674.
[2] XU Jingjing, TAN Yanbin, ZHANG Minming. Medical imaging in tumor precision medicine: opportunities and challenges[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 455-461.
[3] PAN Jingying, HE Mengye, KE Wei, HU Menglin, WANG Meifang, SHEN Peng. Advances on correlation of PET-CT findings with breast cancer molecular subtypes, treatment response and prognosis[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 473-480.
[4] ZHANG Siying, CHEN Feng. Research progress of CT/MRI parametric response map in precision evaluation of therapeutic response of cancer patients[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 468-472.
[5] PAN Yao, CHEN Jieyu, YU Risheng. Accurate imaging diagnosis and evaluation of pancreatic cancer[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 462-467.
[6] WANG Mengyan, ZHU Biao. Research progress on genes mutations related to sulfa drug resistance in Pneumocystis jirovecii[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 563-569.
[7] LI Yandie, LU Meiping. Progress on the study of NLRP3 inflammasome in autoinflammatory diseases of children[J]. Journal of ZheJiang University(Medical Science), 2017, 46(4): 449-453.
[8] WANG Liya, QIAN Yeqing, JIN Fan. Research progress on the safety of offsprings conceived by assisted reproductive technology[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 279-284.
[9] YAN Kai, JIN Fan. Advances on prenatal diagnosis of birth defects associated with genetic disorders[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 227-232.
[10] TANG Minyue, ZHU Yimin. The involvement of galectin-1 in implantation and pregnancy maintenance at the maternal-fetal interface[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 321-327.
[11] FU Xiaohua, XU Weihai, QIU Shengchun, SHU Jing. Research progress on the relationship of brown adipose tissue with polycystic ovary syndrome[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 315-320.
[12] FU Yanling, ZHU Yimin. Potential clinical application of Kisspeptin in reproductive endocrinology[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 328-333.
[13] QIAN Yeqing, WANG Liya, LUO Yuqin, YAN Kai, DONG Minyue, JIN Fan. Advances in the application of high-throughput sequencing in clinical genetics[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 334-337.
[14] SHEN Dan, WANG Fangfang, JIANG Zhou, QU Fan. Long-term effects of polycystic ovary syndrome on the offspring[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 300-304.
[15] HE Yujie,PAN Jianping. Progress on mechanisms for pathogensto evade NOD-like receptor and Toll-like receptor signaling pathways[J]. Journal of ZheJiang University(Medical Science), 2017, 46(2): 218-224.