Published ahead of print on March 24, 2005, doi:10.1164/rccm.200405-652OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200405-652OC
The Role of Hyaluronan Synthase 3 in Ventilator-induced Lung InjuryPulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan; and Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas Correspondence and requests for reprints should be addressed to Deborah A. Quinn, M.D., Pulmonary and Critical Care Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch-148, Boston, MA 02114. E-mail: dquinn1{at}partners.org We recently found that low-molecular-weight hyaluronan was induced by cyclic stretch in lung fibroblasts and accumulated in lungs from animals with ventilator-induced lung injury. The low-molecular-weight hyaluronan produced by stretch increased interleukin-8 production in epithelial cells, and was accompanied by an upregulation of hyaluronan synthase–3 mRNA. We hypothesized that low-molecular-weight hyaluronan induced by high VT was dependent on hyaluronan synthase 3, and was associated with ventilator-induced lung injury. Effects of high VT ventilation in C57BL/6 wild-type and hyaluronan synthase–3 knockout mice were compared. Significantly increased neutrophil infiltration, macrophage inflammatory protein–2 production, and lung microvascular leak were found in wild-type animals ventilated with high VT. These reactions were significantly reduced in hyaluronan synthase–3 knockout mice, except the capillary leak. Wild-type mice ventilated with high VT were found to have increased low-molecular-weight hyaluronan in lung tissues and concomitant increased expression of hyaluronan synthase–3 mRNA, neither of which was found in hyaluronan synthase–3 knockout mice. We conclude that high VT induced low-molecular-weight hyaluronan production is dependent on de novo synthesis through hyaluronan synthase 3, and plays a role in the inflammatory response of ventilator-induced lung injury.
Key Words: hyaluronic acid • knockout mice • mechanical ventilation • tidal volume This article has been cited by other articles:
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