HYALURONIDASE TREATMENT OF ACUTE LYMPHEDEMA IN A MOUSE TAIL MODEL

Abstract

The purpose of this study was to investigatethe impact of hyaluronidase (HAase) onlymphedema using an acute mouse taillymphedema model. Six-week old mice servedto produce acute lymphedema and were theneither treated with HAase injection or usedas operative controls. An additional group ofunmanipulated normal mice was used forcomparison. Tail volumes were measured for23 days and histological changes examined.Western blot analysis was conducted to quantifylymphatic vessel endothelial hyaluronanreceptor (LYVE)-1, tumor necrosis factor(TNF)-α, transforming growth factor(TGF)-ß1, podoplanin, CD 44, and vascularendothelial growth factor receptor3 (VEGFR3)expression levels. The operative control groupshowed an increase in thickness of the dermisand subdermis, microlymphatic dilatation,and an increase in neutrophils. In contrast,the HAase treated group exhibited alleviationof inflammation evidenced by a decline inmicrolymphatic dilatation and neutrophils andan overall increase in microlymphatic vessels.Western blot analysis demonstrated thatTNF-α and TGF-ß1 expression declined butCD44 expression increased in the HAasetreated group. Levels of LYVE1, podoplanin,and VEGFR3 also increased significantly inthe HAase group. Our results indicate thatHAase treatment in the acute mouse tailmodel reduced lymphedema volume possiblythrough degradation of HA trafficking, whichreduced inflammation and fibrosis in tissuesand stimulated lymphangiogenesis.