Anti-inflammatory deficiencies in neutrophilic asthma: reduced galectin-3 and IL-1RA/IL-1β

被引:76
作者
Gao, Peng [1 ,2 ,3 ]
Gibson, Peter G. [2 ,3 ,4 ]
Baines, Katherine J. [2 ,3 ]
Yang, Ian A. [5 ,6 ]
Upham, John W. [5 ,7 ]
Reynolds, Paul N. [8 ,9 ]
Hodge, Sandra [8 ,9 ]
James, Alan L. [10 ,11 ]
Jenkins, Christine [12 ]
Peters, Matthew J. [13 ,14 ]
Zhang, Jie [1 ]
Simpson, Jodie L. [2 ,3 ]
机构
[1] Jilin Univ, Affiliated Hosp 2, Dept Resp Med, Changchun 130023, Jilin, Peoples R China
[2] Hunter Med Res Inst, Dept Resp & Sleep Med, New Lambton Heights, NSW, Australia
[3] Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia
[4] Woolcock Inst Med Res, Glebe, NSW, Australia
[5] Univ Queensland, Sch Med, Brisbane, Qld, Australia
[6] Prince Charles Hosp, Dept Thorac Med, Brisbane, Qld 4032, Australia
[7] Princess Alexandra Hosp, Dept Resp Med, Brisbane, Qld 4102, Australia
[8] Royal Adelaide Hosp, Dept Thorac Med, Adelaide, SA 5000, Australia
[9] Hanson Inst, Lung Res Lab, Adelaide, SA, Australia
[10] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Perth, WA, Australia
[11] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia
[12] George Inst Global Hlth, Sydney, NSW, Australia
[13] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia
[14] Concord Gen Hosp, Dept Thorac Med, Concord, NSW, Australia
关键词
Asthma; Galectin-3; Induced sputum; Neutrophil; Macrophage; IL-1; beta; lectin; C-ASSOCIATED PROTEIN; AIRWAY INFLAMMATION; MURINE MODEL; EXPRESSION; ACTIVATION; HYPERRESPONSIVENESS; IDENTIFICATION; GLYCOPROTEIN; CYTOKINES; CELLS;
D O I
10.1186/s12931-014-0163-5
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
100201 [内科学];
摘要
Background: Galectin-3 (gal-3), a member of the beta-galactoside-binding animal lectins, is involved in the recruitment, activation and removal of neutrophils. Neutrophilic asthma is characterized by a persistent elevation of airway neutrophils and impaired efferocytosis. We hypothesized that sputum gal-3 would be reduced in neutrophilic asthma and the expression of gal-3 would be associated with other markers of neutrophilic inflammation. Methods: Adults with asthma (n = 80) underwent a sputum induction following clinical assessment and blood collection. Sputum was dispersed for a differential cell count and ELISA assessment of gal-3, gal-3 binding protein (BP), interleukin (IL)-1 beta, IL-1 receptor antagonist (RA), IL-8 and IL-6. Gal-3 and gal-3BP immunoreactivity were assessed in mixed sputum cells. Results: Sputum gal-3 (median, (q1, q3)) was significantly reduced in neutrophilic asthma (183 ng/mL (91,287)) compared with eosinophilic (293 ng/mL (188,471), p = 0.021) and paucigranulocytic asthma (399 ng/mL (213,514), p = 0.004). The gal-3/gal-3BP ratio and IL-1RA/IL-1 beta ratio were significantly reduced, while gal-3BP and IL-1 beta were significantly elevated in neutrophilic asthma compared with eosinophilic and paucigranulocytic asthma. Conclusion: Patients with neutrophilic asthma have impairment in anti-inflammatory ratio of gal-3/gal-3BP and IL-1RA/IL-1 beta which provides a further framework for exploration into pathologic mechanisms of asthma phenotypes.
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