title: Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.
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.
authors.affiliation: Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.|Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia.|Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Sarra
authors.initials: S
authors.lastname: Bchir
authors.affiliation: Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.
authors.forename: Hela Ben
authors.initials: HB
authors.lastname: Nasr
authors.affiliation: Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France.|Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bouchet
authors.affiliation: Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benzarti
authors.affiliation: Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Garrouch
authors.affiliation: Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.
authors.forename: Zouhair
authors.initials: Z
authors.lastname: Tabka
authors.affiliation: Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Santos
authors.initials: S
authors.lastname: Susin
authors.affiliation: Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.|Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisia.
authors.forename: Karim
authors.initials: K
authors.lastname: Chahed
authors.affiliation: Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bauvois
mesh_terms: D000328:Adult; D000368:Aged; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood*; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000473:pathology; D000074285:Smokers; D012907:Smoking / Q000009:adverse effects / Q000097:blood
chemical_list: D004792:Enzyme Precursors; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D046912:Multiprotein Complexes; D019272:Leukocyte Elastase; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9
keywords: GOLD; chronic obstructive pulmonary disease; cigarette smoke; matrix metalloproteinase; neutrophil elastase; neutrophil gelatinase-associated lipocalin; serum; systemic inflammation