DEL-1, as an anti-neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma

被引：7

作者：

Jia, Man ^{[1
]}

Fu, Heng ^{[1
]}

Jiang, Xinyu ^{[1
]}

Wang, Lina ^{[1
]}

Xu, Jiayan ^{[1
]}

Barnes, Peter J. ^{[2
]}

Adcock, Ian M. ^{[2
]}

Liu, Yi ^{[3
,4
]}

He, Shujuan ^{[5
]}

Zhang, Fan

Yao, Lei ^{[1
]}

Sun, Peng ^{[1
]}

Yao, Xin ^{[1
]}

机构：

[1] Nanjing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing 210029, Peoples R China

[2] Natl Heart & Lung Inst, Imperial Coll London, Fac Med, Airway Dis Sect, London, England

[3] Shandong First Med Univ, Shandong Prov Hosp, Dept Allergy Pulm & Crit Care Med, Jinan, Peoples R China

[4] Shandong First Med Univ & Shandong Acad Med Sci, Med Sci & Technol Innovat Ctr, Shandong Key Lab Infect Resp Dis, Jinan, Peoples R China

[5] Nanjing Red Cross Hosp, Dept Resp Med, Nanjing, Peoples R China

来源：

ALLERGY | 2024年 / 79卷 / 05期

基金：

中国国家自然科学基金;

关键词：

asthma; bronchial epithelial cells; DEL-1; neutrophil transepithelial migration; DEVELOPMENTAL ENDOTHELIAL LOCUS-1; ADHESION MOLECULES; CELL-ADHESION; GENE-THERAPY; LFA-1; RECRUITMENT; MAC-1; LIPOPOLYSACCHARIDE; DITHIOTHREITOL; EXPRESSION;

D O I：

10.1111/all.15882

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

<bold>Background: </bold>Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus-1 (DEL-1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation. <bold>Methods: </bold>Levels of DEL-1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL-1 modulation of neutrophil adhesion and transepithelial migration was examined in a co-culture model in vitro. The effects of DEL-1-adenoviral vector-mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)-induced neutrophilic asthma were studied in mice in vivo. <bold>Results: </bold>DEL-1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL-1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 +/- 75.3 vs. 276.8 +/- 29.36 pg/mL, p < .001) and were negatively correlated to blood neutrophils (r = -0.2881, p = .0384) and neutrophil-to-lymphocyte ratio (NLR) (r = -0.5469, p < .0001). DEL-1 concentrations in the EBC of severe asthmatic patients (113.2 +/- 8.09 pg/mL) were also lower than normal subjects (193.0 +/- 7.61 pg/mL, p < .001) and were positively correlated with the asthma control test (ACT) score (r = 0.3678, p = .0035) and negatively related to EBC IL-17 (r = -0.3756, p = .0131), myeloperoxidase (MPO) (r = -0.5967, p = .0055), and neutrophil elastase (NE) (r = -0.5488, p = .0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA-1 binding to ICAM-1 and inhibited by DEL-1. DEL-1 mRNA and protein expression in human bronchial epithelial cells were regulated by IL-17. Exogenous DEL-1 inhibited IL-17-enhanced neutrophil adhesion and migration. DEL-1 expression was decreased while neutrophil infiltration was increased in the airway of a murine model of neutrophilic asthma. This was prevented by DEL-1 overexpression. <bold>Conclusions: </bold>DEL-1 down-regulation leads to increased neutrophil migration across bronchial epithelial cells and is associated with neutrophilic airway inflammation in asthma.

引用

页码：1180 / 1194

页数：15