Pasteurella multocida toxin increases endothelial permeability via Rho kinase and myosin light chain phosphatase

Markus Essler, Karin Hermann, Mutsuki Amano, Kozo Kaibuchi, Jürgen Heesemann, Peter C. Weber, Martin Aepfelbacher

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Pasteurella multocida toxin (PMT) has been shown to induce actin reorganization through activation of the GTPase Rho. Here we investigated the involvement of the Rho target proteins Rho kinase and myosin light chain (MLC) phosphatase in the PMT-induced increase in endothelial permeability and the underlying actin reorganization of endothelial cells, stimulation of endothelial layers With PMT enhanced transendothelial permeability > 10- fold, and this was abolished by pretreatment with the specific Rho inactivator C3 transferase from Clostridium botulinum. The PMT-induced increase in endothelial permeability was associated with 1) inactivation of MLC phosphatase, 2) an increase in MLC phosphorylation, and 3) endothelial cell retraction and actin stress fiber formation. PMT-stimulated actin reorganization could be prevented by 1) pretreatment of cells with C3 transferase, 2) microinjection of the Rho binding domain and the pleckstrin homology domain of Rho kinase, and 3) microinjection of constitutively active MLC phosphatase. Together, these results suggest that PMT activates Rho/Rho kinase, which inactivates MLC phosphatase. The resulting increase in MLC phosphorylation causes endothelial cell retraction and a rise in endothelial permeability.

Original languageEnglish
Pages (from-to)5640-5646
Number of pages7
JournalJournal of Immunology
Volume161
Issue number10
Publication statusPublished - 15-11-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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