Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury.pdfVIP

Int. J. Med. Sci. 2009, 6 9 International Journal of Medical Sciences 2009; 6(1):9-17 ? Ivyspring International Publisher. All rights reserved Research Paper Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury Michele YF Kong1 , Amit Gaggar2,3, Yao Li1, Margaret Winkler1, J Edwin Blalock3, and JP Clancy1 1. Departments of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA 2. Departments of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35233, USA 3. Departments of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA Correspondence to: Michele YF Kong, MD, Suite 504, 1600 7th Avenue South, Birmingham AL 35233. Phone: 205-939-9387; Fax: 205-975 6505; Email: mkong@ Received: 2008.09.11; Accepted: 2008.12.15; Published: 2008.12.16 Abstract Pediatric Acute Lung Injury (ALI) is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pedi- atric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. Tissue Inhibitor of Matrix metalloproteinase-1 (TIMP-1), a natural inhibitor of MMPs was detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to controls. In subjects who remained intubated for ≥10 days, MMP-9 activity decreased, with 80% found in the latent form. In contrast, almost all MMP-8 detected at later disease course was constitutively active. Discriminating MMP-9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results identify a specific repertoire of MMP isoforms in the lung secretions of pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with protracted disease. Key words: matrix met