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International Journal of Cell Biology
Volume 2015, Article ID 712507, 15 pages
Review Article

The Rise and Fall of Hyaluronan in Respiratory Diseases

1Pediatric Institute, Cleveland Clinic, Cleveland, OH 44195, USA
2Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA
3Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA
4Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, OH 44195, USA
5National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
6Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA

Received 13 October 2014; Revised 11 February 2015; Accepted 3 May 2015

Academic Editor: Arnoud Sonnenberg

Copyright © 2015 Mark E. Lauer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.