Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis.
Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We first performed zymographic analysis to identify the profile of MMPs. Zymography revealed a similar MMPs profile in all populations studied and that MMP-9 was the major enzyme released. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated whether airflow limitation may be associated with an imbalance between these enzymes. MMP-9 and TIMP-1 concentrations were greater in sputum of patients with asthma and chronic bronchitis than in control subjects. The molar ratio between MMP-9 and TIMP-1 was lower in asthmatics and chronic bronchitics than in control subjects, and positively correlated with FEV1 values. In asthma, MMP-9 levels were significantly correlated with the number of macrophages and neutrophils. This study shows that airway inflammation in asthma and chronic bronchitis is associated with an imbalance between MMP-9 and TIMP-1 which may have a role in the pathogenesis of ECM remodeling and airflow obstruction.
Vignola
A M
AM
Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo; Istituto di Medicina Generale e Pneumologia, Università di Palermo, Palermo, Italy.
Riccobono
L
L
Mirabella
A
A
Profita
M
M
Chanez
P
P
Bellia
V
V
Mautino
G
G
D'accardi
P
P
Bousquet
J
J
Bonsignore
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001249:Asthma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001991:Bronchitis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005541:Forced Expiratory Volume / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D008264:Macrophages / Q000473:pathology; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D011480:Protease Inhibitors / Q000032:analysis*; D012123:Pulmonary Ventilation / Q000502:physiology; D012967:Sodium Dodecyl Sulfate; D013183:Sputum / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D013501:Surface-Active Agents; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*
D011480:Protease Inhibitors; D013501:Surface-Active Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D012967:Sodium Dodecyl Sulfate; D003094:Collagen; D017364:Collagenases; D020780:Matrix Metalloproteinase 9