Serum matrix metalloproteinases in adult CF patients: Relation to pulmonary exacerbation

Abstract 

Background

Matrix metalloproteinases (MMPs) virtually degrade all components of the extracellular matrix and are mainly expressed in tissues following inflammation or remodeling. Increased expression of certain MMPs in sputum and bronchoalveolar lavage of patients with cystic fibrosis (CF) is related to impaired lung function. We investigated whether a panel of serum MMPs is associated with both, impairment of pulmonary function and occurrence of pulmonary exacerbations (PEx) in adult patients with CF.

Methods

Serum concentrations of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, and TIMP-1 were determined by ELISA in 54 adult CF patients. PEx was defined based on a score established by Rosenfeld in 2001. MMP-1, MMP-8, MMP-9 and TIMP-1 were assessed in 7 CF patients with PEx before and after systemic antibiotic therapy.

Results

Of the 54 CF patients, PEx was diagnosed in 16 different CF patients. Compared to healthy controls, MMP-1, MMP-8, and MMP-9, serum levels were elevated in CF patients and correlated with PEx. MMP-8 expression was associated with impaired lung function. For MMP-2, we observed a decreased expression and an association of MMP-2 decline with PEx. Antibiotic treatment of CF patients with PEx led to a decrease of MMP-1, MMP-8 and active MMP-9 protein concentration.

Conclusions

Increased serum expression of certain MMPs is associated with occurrence of PEx and impaired lung function in CF. Hence, these MMPs might serve as surrogate markers for PEx.

Abbreviations: ALI, acute lung injury, ARDS, adult respiratory distress syndrome, BAL, bronchoalveolar lavage, BMI, body-mass-index, COPD, chronic obstructive pulmonary disease, CRP, C-reactive protein, CF, cystic fibrosis, ECM, extracellular matrix, FEV₁, forced expiratory volume in one second, MEF₂₅, maximum expiratory flow rate at 25% vital capacity, MMP, matrix metalloproteinases, TIMP, tissue inhibitor of metalloproteinases, PCT, procalcitonin, PEx, pulmonary exacerbation, pCO₂, partial pressure of carbon dioxide, pO₂, partial pressure of oxygen, VC, vital capacity

Keywords: Cystic fibrosis, Inflammation, Lung, Matrix metalloproteinases, Tissue inhibitors of metalloproteinases