title: The role of hyaluronan synthase 3 in ventilator-induced lung injury.
abstract: 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.
authors.affiliation: Pulmonary and Critical Care Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch-148, Boston, MA 02114, USA.
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Bai
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Spicer
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Mascarenhas
authors.forename: Lunyin
authors.initials: L
authors.lastname: Yu
authors.forename: Cristhiaan D
authors.initials: CD
authors.lastname: Ochoa
authors.forename: Hari G
authors.initials: HG
authors.lastname: Garg
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Quinn
mesh_terms: D000465:Algorithms; D000818:Animals; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D000076002:Hyaluronan Synthases; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008171:Lung Diseases / Q000201:enzymology / Q000209:etiology; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D013990:Tidal Volume
chemical_list: D054426:Chemokine CXCL2; D016209:Interleukin-8; D015846:Monokines; D014453:Glucuronosyltransferase; C491356:Has3 protein, mouse; D000076002:Hyaluronan Synthases