Transduction of PTEN into Eosinophils Attenuates Survival, Chemotaxis, and Airway Inflammation

Abstract

PTEN is part of a complex signaling system that affects a variety of important cell functions. It has been shown that PTEN negatively regulates cell functions, such as proliferation, survival, and migration, in tumor and immune cells. Moreover, intratracheal administration of adenoviruses carrying PTEN cDNA inhibits OVA-induced eosinophilic inflammation and bronchial hyperresponsiveness in a murine model of asthma. In the present study, we utilized TAT-fused protein transduction system to clarify the role of PTEN in eosinophils and allergic inflammation. A small region of the HIV TAT protein (YGRKKRRQRRR), a protein transduction domain known to enter mammalian cells efficiently, was fused to the N-terminus of PTEN. Eosinophil survival was analyzed by flow cytometry stained with Annexin V and propidium iodide. Chemotaxis assay was performed using Boyden chamber. BALF cell analysis and histological examination was performed using OVA-challenged A/J mice. TAT-PTEN, but not control protein TAT-GFP, blocked the ability of IL-5 to prevent apoptosis of eosinophils from allergic subjects. The eotaxin-induced eosinophil chemotaxis was inhibited by TAT-PTEN in a dose-dependent manner. Intratracheal pretreatment of TAT-PTEN, but not TAT-GFP, significantly inhibited the OVA-induced eosinophil infiltration in BALF. Histological examination of the lung including HE and alcian blue/PAS stainings revealed that TAT-PTEN, but not TAT-GFP, abrogated eosinophilic inflammation and mucus production. Our results suggest that PTEN negatively regulates eosinophil survival, chemotaxis, and allergic inflammation. The pharmacological targeting of PTEN may be a new strategy to treat eosinophilic disorders.