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The lectin‐like domain of TNF, but not cAMP, protects from Listeriolysin O‐induced endothelial hyperpermeability
Author(s) -
Xiong Chenling,
Yang Guang,
Kumar Sanjiv,
Black Stephen,
Verin Alexander,
Catravas John,
Fischer Bernhard,
Chakraborty Trinad,
Lucas Rudolf
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb389
Subject(s) - listeriolysin o , endothelial stem cell , phosphorylation , in vivo , chemistry , peptide , microbiology and biotechnology , biology , biochemistry , listeria monocytogenes , in vitro , listeria , genetics , bacteria
Listeriosis can lead to potentially lethal pulmonary permeability edema in newborns and immune‐compromised patients. Listeriolysin‐O (LLO), the main virulence factor of L. monocytogenes , induces a dose‐dependent myosin light chain (MLC) phosphorylation and hyperpermeability in human lung microvascular endothelial cells (HL‐MVEC), which can promote edema formation. The lectin‐like domain of TNF is spatially distinct from the TNF receptor binding sites and can be mimicked by the 17 amino acid TIP peptide. This peptide was shown to reduce pulmonary edema formation in in vivo and in situ murine and rabbit models. The objective of this study was to investigate, using electrical cell‐substrate impedance sensing (ECIS) and Western Blotting techniques, whether the TIP peptide can protect from LLO‐induced endothelial hyperpermeability in HL‐MVEC. In contrast to a cell‐permeant cAMP analogue, the TIP peptide blunts LLO‐induced hyperpermeability in monolayers of HL‐MVEC, as measured in ECIS. The peptide moreover inhibits LLO‐mediated MLC phosphorylation (Western Blotting) and blocks LLO‐induced generation of reactive oxygen species (EPR measurements), which increase endothelial permeability. These results indicate that the lectin‐like domain of TNF has a potential therapeutic value in protecting from LLO‐induced endothelial hyperpermeability and subsequent pulmonary permeability edema.