Different contributions of clathrin- and caveolae-mediated endocytosis of vascular endothelial cadherin to lipopolysaccharide-induced vascular hyperpermeability

PLoS One. 2014 Sep 2;9(9):e106328. doi: 10.1371/journal.pone.0106328. eCollection 2014.

Abstract

Vascular hyperpermeability induced by lipopolysaccharide (LPS) is a common pathogenic process in cases of severe trauma and sepsis. Vascular endothelial cadherin (VE-cad) is a key regulatory molecule involved in this process, although the detailed mechanism through which this molecule acts remains unclear. We assessed the role of clathrin-mediated and caveolae-mediated endocytosis of VE-cad in LPS-induced vascular hyperpermeability in the human vascular endothelial cell line CRL-2922 and determined that vascular permeability and VE-cad localization at the plasma membrane were negatively correlated after LPS treatment. Additionally, the loss of VE-cad at the plasma membrane was caused by both clathrin-mediated and caveolae-mediated endocytosis. Clathrin-mediated endocytosis was dominant early after LPS treatment, and caveolae-mediated endocytosis was dominant hours after LPS treatment. The caveolae-mediated endocytosis of VE-cad was activated through the LPS-Toll-like receptor 4 (TLR4)-Src signaling pathway. Structural changes in the actin cytoskeleton, specifically from polymerization to depolymerization, were important reasons for the switching of the VE-cad endocytosis pathway from clathrin-mediated to caveolae-mediated. Our findings suggest that clathrin-mediated and caveolae-mediated endocytosis of VE-cad contribute to LPS-induced vascular hyperpermeability, although they contribute via different mechanism. The predominant means of endocytosis depends on the time since LPS treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Cadherins / metabolism*
  • Capillary Permeability / drug effects*
  • Caveolae / drug effects
  • Caveolae / metabolism*
  • Cell Line
  • Clathrin / metabolism*
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Endocytosis / drug effects*
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antigens, CD
  • Cadherins
  • Clathrin
  • Lipopolysaccharides
  • cadherin 5

Grant support

This study was supported by the "12th Five-Year Plan" National Science and Technology Support Program of China (grant number 2012BAI11B01) and Key Project of 12th Five-Year Military Plan (grant number BWS12J033). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.