International Journal of Medical Sciences

11 February 2012

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Int J Med Sci 2009; 6(1):9-17. doi:10.7150/ijms.6.9

Research Paper

Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury

Michele YF Kong1 ✉, Amit Gaggar2,3, Yao Li1, Margaret Winkler1, J Edwin Blalock3, 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

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 pediatric 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.

Keywords: matrix metalloproteinases, acute lung injury, pediatric, viral infection

How to cite this article:
Kong MYF, Gaggar A, Li Y, Winkler M, Blalock JE, Clancy JP. Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury. Int J Med Sci 2009; 6(1):9-17. Available from http://www.medsci.org/v06p0009.htm