Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

Sarra Bchir,Zouhair Tabka,Brigitte Bauvois,Hela Ben Nasr,Abdelhamid Garrouch,Mohamed Benzarti,Karim Chahed,Santos Susin,Sandrine Bouchet

doi:10.1111/jcmm.13057

Abstract

A growing body of evidence points towards smoking‐related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase‐9 (pro‐ and active MMP‐9), neutrophil gelatinase‐associated lipocalin (NGAL) and the proMMP‐9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable‐phase COPD patients (82 smokers, 18 never‐smokers) and 28 healthy adults (21 smokers, 7 never‐smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP‐9, NGAL and proMMP‐9/NGAL in COPD smokers. While the triad discriminated between smokers and non‐smokers in the COPD group, MMP‐9 and proMMP‐9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack‐years did not alter the findings. Serum MMP‐9, NGAL and proMMP‐9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP‐3 (but not of IL‐6 and MMP‐12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack‐years. Among COPD smokers, levels of MMP‐9, NGAL and proMMP‐9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP‐9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP‐9, NGAL, proMMP‐9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking.

Highlights

chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways and the lung parenchyma, leading to progressive, partially reversible or irreversible airway constriction [1, 2]
In the present study of a well-characterized cohort of healthy and COPD smokers and non-smokers, we observed that serum levels of MMP-9, neutrophil gelatinase-associated lipocalin (NGAL) and proMMP-9/NGAL were higher in COPD smokers than in COPD non-smokers
Whereas levels of MMP-9 and the proMMP-9/ NGAL complex discriminate between COPD smokers and healthy smokers, NGAL appears to be a marker of smoking status

Summary

Introduction

COPD is characterized by chronic inflammation of the airways and the lung parenchyma, leading to progressive, partially reversible or irreversible airway constriction [1, 2]. Contrasting findings have been reported in other studies of patients with COPD, where (i) increased levels of serum MMP-9 were not related to the decline in FEV1 [23,24,25] or (ii) lower levels of serum MMP-9 correlated with the disease severity [26]. These studies did not take into account the amount of MMP-9 protein in the latent or active form [12, 17, 21,22,23,24,25,26]. MMP-9 blood levels did not differ when comparing current smokers and exsmokers with COPD [15], differences between smokers and nonsmokers have been observed in studies of healthy adults [30] and patients with COPD [22, 31]

Methods

Results

Conclusion