Abstract 1638: Targeted Deletion Of Endothelial Lipase Protects Against Allergic Asthma Through Raising Plasma HDL Level And Attenuating Eosinophil Infiltration
Background: High-density lipoprotein cholesterol (HDL-C) has a variety of anti-inflammatory properties. Endothelial lipase (EL) is a novel phospholipase and a physiological regulator of plasma HDL-C levels. In this study, we investigated the role of HDL-C in allergic inflammation in the lung using EL-deficient (EL-KO) mice that have the high level of plasma HDL-C.
Methods and Results: EL-KO and wild-type control mice were sensitized and challenged with ovalbumin to induce allergic asthma. In wild-type mice, EL was expressed in epithelial cells, alveolar type II cells, as well as endothelial cells in the lung, and the expression is upregulated during the ovalbumin-induced inflammation. The number of eosinophils in bronchoalveolar lavage and the expression of vascular cell adhesion molecule-1 (VCAM-1) were lower in EL-KO than in control mice, concomitant with attenuated hypercontraction of the airway smooth muscle cells. HDL reduced the cytokine-induced VCAM-1 expression in cultured endothelial cells. These findings suggest that high levels of HDL-C in EL-KO mice inhibited allergic inflammation in the lung. When plasma HDL levels were decreased to the similar levels in both mouse groups by adenovirus-mediated overexprssion of EL, however, the eosinophil infiltration was still lower in EL-KO mice. In vitro adhesion assay revealed that EL overexpression on the surface of COS7 cells resulted in an enhancement of the eosinophil binding, which is abolished by addition of heparin. The finding indicates that EL mediates the binding of eosinophils to the vascular endothelium through its ligand-binding function.
Conclusions: Targeted deletion of EL protects against allergic inflammation in the lung, and the protective effects in EL-KO mice were likely to be mediated through high plasma HDL levels, downregulation of VCAM-1, and loss of the direct ligand-binding functions. Thus, EL plays an important role in the genesis of inflammatory diseases including allergic asthma.