RRC ID 3818
Author Adachi T, Hanaka S, Masuda T, Yoshihara H, Nagase H, Ohta K.
Title Transduction of phosphatase and tensin homolog deleted on chromosome 10 into eosinophils attenuates survival, chemotaxis, and airway inflammation.
Journal J. Immunol.
Abstract Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN antagonizes the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. In the present study, we used a TAT fusion protein transduction system to elucidate the role of PTEN in eosinophils and airway 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. Flow cytometric analysis of annexin V- and propidium iodide-stained cells was used to assess eosinophil survival. A chemotaxis assay was performed using a Boyden chamber. Cell analysis in bronchoalveolar lavage fluid and histological examinations were performed using OVA-challenged A/J mice. We found that TAT-PTEN was successfully internalized into eosinophils and functioned as a phosphatase in situ. TAT-PTEN, but not a TAT-GFP control protein, blocked the ability of IL-5 to prevent the apoptosis of eosinophils from allergic subjects. The eotaxin-induced eosinophil chemotaxis was inhibited by TAT-PTEN in a dose-dependent manner. Intranasal pretreatment with TAT-PTEN, but not TAT-GFP, significantly inhibited the OVA-induced eosinophil infiltration in bronchoalveolar lavage fluid. Histological examination of the lung, including H&E and Alcian blue/periodic acid-Schiff staining, 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 constitute a new strategy for the treatment of eosinophilic disorders.
Volume 179(12)
Pages 8105-11
Published 2007-12-15
PII 179/12/8105
PMID 18056352
MeSH Amino Acid Sequence Animals Cell Survival Chemotaxis* Eosinophils / enzymology Eosinophils / immunology* Humans Mice Mice, Inbred Strains Molecular Sequence Data PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism* Pneumonia / immunology* Pneumonia / pathology Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transduction, Genetic tat Gene Products, Human Immunodeficiency Virus / genetics tat Gene Products, Human Immunodeficiency Virus / metabolism
IF 4.718
Times Cited 9
DNA material pAxCAhPTEN1(RDB02013)