Functional activity of peripheral blood eosinophils in allergen-induced late-phase airway inflammation in asthma patients

Journal of Inflammation

Raimundas Sakalauskas¹  Deimante Hoppenot¹  Jolanta Jeroch¹  Kestutis Malakauskas¹  Simona Lavinskiene¹ 

[1] Department of Pulmonology and Immunology, Lithuanian University of Health Sciences, Kaunas, Lithuanian

关键词: ROS;    Chemotaxis;    Apoptosis;    Allergic asthma;    Airway inflammation;    Eosinophils;   

Others  :  1148095
DOI  :  10.1186/s12950-015-0065-4

 received in 2014-09-24, accepted in 2015-02-27,  发布年份 2015

【 摘 要 】

Objective

We aimed to investigate peripheral blood eosinophil chemotaxis, generation of spontaneous reactive oxygen species (ROS), and apoptosis in patients with allergic asthma after bronchial allergen challenge.

Material and methods

A total of 18 patients with allergic asthma (AA), 14 with allergic rhinitis (AR), and 10 healthy subjects (HS) underwent bronchial challenge with a specific allergen extract. Eosinophils from peripheral blood were isolated 24 h before as well as 7 and 24 h after bronchial allergen challenge. Chemotaxis, spontaneous ROS production in eosinophils, and apoptosis were analyzed by flow cytometry. Serum and induced sputum IL-5 levels were measured by ELISA; the cell count in sputum was analyzed by the May-Grünwald-Giemsa method.

Results

Before bronchial allergen challenge, peripheral blood eosinophil chemotaxis, spontaneous ROS production was enhanced and eosinophil apoptosis was reduced in the patients with AA as compared with AR patients and HS (P < 0.05). Meanwhile, eosinophil chemotaxis and ROS generation markedly increased in the patients with AA 7 h and 24 h after challenge compared with other groups and baseline values (P < 0.05). The percentage of apoptotic eosinophils in the patients with AA decreased at 7 h as well as 24 h after challenge when compared with other groups and the baseline values (P < 0.05). There was a significant correlation between the migrated peripheral blood eosinophil count and the sputum eosinophil count (Rs = 0.89, P < 0.0001) and the sputum IL-5 level (Rs = 0.68, P = 0.002) at 24 h after bronchial challenge only in the patients with AA. Furthermore, the percentage of peripheral blood apoptotic eosinophils significantly correlated with eosinophil count in sputum (Rs = −0.53, P = 0.02), and ROS production correlated with the serum IL-5 levels (Rs = 0.71, P = 0.01).

Conclusion

During allergen-induced late-phase airway inflammation, peripheral blood eosinophils demonstrated further alterations of their functional activity manifested by enhanced spontaneous ROS production, increased chemotaxis, and diminished apoptosis in patients with AA.

【 授权许可】

   
2015 Lavinskiene et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Spina D, Page CP: Asthma – a need for a rethink? Trends Pharmacol Sci 2002, 23(7):311-5.
• [2]Lintomen L, Franchi G, Nowill A, Condino-Neto A, de Nucci G, Zanesco A, et al.: Human eosinophil adhesion and degranulation stimulated with eotaxin and RANTES in vitro: lack of interaction with nitric oxide. BMC Pulm Med 2008, 8:13. BioMed Central Full Text
• [3]Jarjour NN, Calhoun WJ, Kelly EA, Gleich GJ, Schwartz LB, Busse WW: The immediate and late allergic response to segmental bronchopulmonary provocation in asthma. Am J Respir Crit Care Med 1997, 155(5):1515-21.
• [4]Kotsimbos AT, Hamid Q: IL-5 and IL-5 receptor in asthma. Mem Inst Oswaldo Cruz 1997, 92(Suppl 2):75-91.
• [5]Liu LY, Sedgwick JB, Bates ME, Vrtis RF, Gern JE, Kita H, et al.: Decreased expression of membrane IL-5 receptor alpha on human eosinophils: I. Loss of membrane IL-5 receptor alpha on airway eosinophils and increased soluble IL-5 receptor alpha in the airway after allergen challenge. J Immunol 2002, 169(11):6452-8.
• [6]Rosenberg HF, Phipps S, Foster PS: Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol 2007, 119(6):1303-10. quiz 11–2
• [7]Garcia G, Taille C, Laveneziana P, Bourdin A, Chanez P, Humbert M: Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev 2013, 22(129):251-7.
• [8]Barthel SR, Jarjour NN, Mosher DF, Johansson MW: Dissection of the hyperadhesive phenotype of airway eosinophils in asthma. Am J Respir Cell Mol Biol 2006, 35(3):378-86.
• [9]Wardlaw AJ: Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm. J Allergy Clin Immunol 1999, 104(5):917-26.
• [10]Wardlaw AJ: The role of adhesion in eosinophil function. Chem Immunol 2000, 78:93-111.
• [11]Plotz SG, Traidl-Hoffmann C, Feussner I, Kasche A, Feser A, Ring J, et al.: Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators. J Allergy Clin Immunol 2004, 113(6):1152-60.
• [12]Teran LM, Noso N, Carroll M, Davies DE, Holgate S, Schroder JM: Eosinophil recruitment following allergen challenge is associated with the release of the chemokine RANTES into asthmatic airways. J Immunol 1996, 157(4):1806-12.
• [13]Barnes PJ: Reactive oxygen species and airway inflammation. Free Radic Biol Med 1990, 9(3):235-43.
• [14]Sannohe S, Adachi T, Hamada K, Honda K, Yamada Y, Saito N, et al.: Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis. Eur Respir J 2003, 21(6):925-31.
• [15]Sedgwick JB, Geiger KM, Busse WW: Superoxide generation by hypodense eosinophils from patients with asthma. Am Rev Respir Dis 1990, 142(1):120-5.
• [16]Walsh GM: Mechanisms of human eosinophil survival and apoptosis. Clin Exp Allergy 1997, 27(5):482-7.
• [17]Ilmarinen P, Kankaanranta H: Eosinophil apoptosis as a therapeutic target in allergic asthma. Basic Clin Pharmacol Toxicol 2014, 114(1):109-17.
• [18]Kankaanranta H, Lindsay MA, Giembycz MA, Zhang X, Moilanen E, Barnes PJ: Delayed eosinophil apoptosis in asthma. J Allergy Clin Immunol 2000, 106(1 Pt 1):77-83.
• [19]Global initiative for asthma (GINA): Global strategy for asthma management and prevention: NHLBI/WHO workshop report. National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda; 2002.
• [20]Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al.: Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008, 63(Suppl 86):8-160.
• [21]Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, et al.: Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012, 67(1):18-24.
• [22]Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al.: Interpretative strategies for lung function tests. Eur Respir J 2005, 26(5):948-68.
• [23]Baur X, Huber H, Degens PO, Allmers H, Ammon J: Relation between occupational asthma case history, bronchial methacholine challenge, and specific challenge test in patients with suspected occupational asthma. Am J Ind Med 1998, 33(2):114-22.
• [24]Pease JE, Williams TJ: Eotaxin and asthma. Curr Opin Pharmacol 2001, 1(3):248-53.
• [25]Kampen GT, Stafford S, Adachi T, Jinquan T, Quan S, Grant JA, et al.: Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood 2000, 95(6):1911-7.
• [26]Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ: Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995, 182(4):1169-74.
• [27]Jiang L, Diaz PT, Best TM, Stimpfl JN, He F, Zuo L: Molecular characterization of redox mechanisms in allergic asthma. Ann Allergy Asthma Immunol 2014, 113(2):137-42.
• [28]Shult PA, Graziano FM, Busse WW: Enhanced eosinophil luminol-dependent chemiluminescence in allergic rhinitis. J Allergy Clin Immunol 1986, 77(5):702-8.
• [29]Wood LG, Gibson PG, Garg ML: Biomarkers of lipid peroxidation, airway inflammation and asthma. Eur Respir J 2003, 21(1):177-86.
• [30]Giembycz MA, Lindsay MA: Pharmacology of the eosinophil. Pharmacol Rev 1999, 51(2):213-340.
• [31]Walsh GM: Eosinophil apoptosis: mechanisms and clinical relevance in asthmatic and allergic inflammation. Br J Haematol 2000, 111(1):61-7.
• [32]Evans DJ, Lindsay MA, O'Connor BJ, Barnes PJ: Priming of circulating human eosinophils following late response to allergen challenge. Eur Respir J 1996, 9(4):703-8.
• [33]Druilhe A, Wallaert B, Tsicopoulos A, Silva JR L e, Tillie-Leblond I, Tonnel AB, et al.: Apoptosis, proliferation, and expression of Bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics. Am J Respir Cell Mol Biol 1998, 19(5):747-57.
• [34]Vignola AM, Chanez P, Chiappara G, Siena L, Merendino A, Reina C, et al.: Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis. J Allergy Clin Immunol 1999, 103(4):563-73.