Increased matrix metalloproteinase-9 in the airway after allergen challenge

Persistent asthma is associated with airway inflammation, tissue damage, an d deposition of extracellular matrix (ECM) proteins, which may be mediated, in part, through release of matrix metalloproteinases (MMPs) and tissue in hibitor of metalloproteinase-1 (TIMP-1). To investigate the role of allerge n in the induction of MMP-9 and TIMP-1, bronchoscopy and segmental bronchop rovocation (SBP) with saline (SAL) and antigen (AG) were performed in 17 al lergic subjects. Bronchoalveolar lavage (BAL) was done 5 min and 48 h after challenge and concentrations of MMP-9 and TIMP-1 in BAL fluid (BALF) were measured by ELISA, Forty-eight hours after AC challenge, concentrations of MMP-9 and TIMP-1 were increased in the airway, but not in serum. Zymography demonstrated that MMP-9 was the predominant metalloproteinase and was pres ent in a latent preform. MMP-9 immunoreactivity was associated primarily wi th neutrophils, and concentrations of MMP-9 in BALF correlated with airway neutrophils and, to a lesser extent, with alveolar macrophages. These data suggest that AG challenge leads to generation of factors, including MMP-9, that may be associated with the initiation of bronchial injury, which may t hen lead to remodeling in asthma.