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Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucortcoids
Cundall, M; Sun, YC; Miranda, C; Trudeau, JB; Barnes, S; Wenzel, SE
关键词Matrix Metalloproteinase-9 Neutrophil Gelatinase-associated Lipocalin Glucocorticoids Asthma Bronchoalveolar Lavage
刊名JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
2003-12-01
DOI10.1016/j.jaci.2003.08.013
112期:6页:1064-1071
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Allergy ; Immunology
研究领域[WOS]Allergy ; Immunology
关键词[WOS]OBSTRUCTIVE PULMONARY-DISEASE ; BRONCHOALVEOLAR LAVAGE FLUID ; TISSUE INHIBITOR ; ALVEOLAR MACROPHAGES ; AIRWAY INFLAMMATION ; ALLERGEN CHALLENGE ; PERIPHERAL-BLOOD ; METALLOPROTEINASE-1 ; SPUTUM ; EXPRESSION
英文摘要

Background: Matrix metalloproteinase (MMP)-9 levels are increased in bronchoalveolar lavage (BAL) fluid from patients with severe asthma on high doses of glucocorticoids (GCs). Objective: We sought to identify neutrophils as the source of increased BAL fluid MMP-9 in severe asthma and to evaluate the effects of GCs on this MMP-9.

Methods: MMP-9 protein, activity, and mRNA were measured in BAL fluid and cells at baseline, and after in vitro GCs in patients with severe asthma and controls using enzyme immunoassays, zymography, Western blotting, and real-time PCR.

Results: The high molecular weight (HMW) form of MMP-9 was significantly increased in severe asthma (P = .02). Western blotting confirmed a heterodimer of MMP-9 and neutrophil gelatinase-associated lipocalin. The HMW MMP-9 correlated with BAL neutrophils (r = .65, P < .0001). BAL cell supernatant MMP-9 protein levels also tended to be higher in patients with severe asthma (overall, P = .09), whereas the HMW activity form was increased (P = .03). MMP-9 protein (and HMW activity) correlated with neutrophils in the cell pellet (r = .75, P < .0001). In contrast to protein and activity, BAL cell mRNA levels were marginally lower in patients with severe asthma than in control subjects (overall, P = .06). Although GCs decreased BAL cell MMP-9 protein and mRNA in vitro, the effect was significantly smaller in severe asthma (P < .01 for both). GCs decreased the pro-MMP-9 activity in patients with severe asthma and normal control subjects, while having no effects on the HMW form (P = .22). Peripheral blood neutrophil MMP-9 protein was not affected by GCs.

Conclusions: BAL neutrophils contribute to BAL fluid MMP-9 protein and activity and are poorly inhibited by GCs.

语种英语
WOS记录号WOS:000187154200006
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被引频次:80[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56752
专题北京大学第三临床医学院_呼吸科
作者单位1.Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA
2.Univ Colorado, Hlth Sci Ctr, Denver, CO USA
3.Peking Univ, Hosp 3, Dept Resp Med, Beijing 100871, Peoples R China
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GB/T 7714
Cundall, M,Sun, YC,Miranda, C,et al. Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucortcoids[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,2003,112(6):1064-1071.
APA Cundall, M,Sun, YC,Miranda, C,Trudeau, JB,Barnes, S,&Wenzel, SE.(2003).Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucortcoids.JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,112(6),1064-1071.
MLA Cundall, M,et al."Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucortcoids".JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 112.6(2003):1064-1071.
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