Deletion of myosin light chain kinase in endothelial cells has a minor effect on the lipopolysaccharide-induced increase in microvascular endothelium permeability in mice

FEBS J. 2012 Apr;279(8):1485-94. doi: 10.1111/j.1742-4658.2012.08541.x. Epub 2012 Mar 16.

Abstract

There is a current view that myosin light chain kinase (MLCK) plays a critical role in endothelial permeability. To investigate the functions of MLCK in endothelial cells in vivo, we generated a mouse model in which MLCK was selectively deleted by crossing Mylk1 floxed mice with Tie2/cre transgenic mice. Knocking out Mylk1 from endothelial cells had no effect on the global phenotype of the mice, including body weight and blood pressure. Lipopolysaccharide (LPS)-mediated septic death was also not altered in the knockout (KO) mice. Consistently, LPS-induced inflammatory injury and the increase in microvascular permeability in the main organs, including the lung and the kidney, was not significantly attenuated in KO mice as compared with wild-type mice. However, the LPS-induced microvascular hyperpermeability of the esophagus and the eyeballs was attenuated in KO mice. We also found that the LPS-mediated increase in the number of caveolae in the endothelial cells of the esophagus was significantly reduced in KO mice. Our results do not support a role for endothelial cell MLCK in the pathogenesis of inflammatory diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillary Permeability / drug effects*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Esophagus / cytology
  • Esophagus / metabolism
  • Eye / cytology
  • Eye / metabolism
  • Female
  • Inflammation / enzymology*
  • Inflammation / etiology
  • Inflammation / mortality
  • Integrases / metabolism
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myosin-Light-Chain Kinase / physiology*
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, TIE-2
  • Survival Rate

Substances

  • Lipopolysaccharides
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2
  • Tek protein, mouse
  • Myosin-Light-Chain Kinase
  • Cre recombinase
  • Integrases