Bone marrow-derived progenitor cells prevent thrombin-induced increase in lung vascular permeability

Yidan D. Zhao, Hiroshi Ohkawara, Stephen M. Vogel, Asrar B. Malik, You Yang Zhao

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Since thrombin activation of endothelial cells (ECs) is well-known to increase endothelial permeability by disassembly of adherens junctions (AJs) and actinomyosin contractility mechanism involving myosin light chain (MLC) phosphorylation, we investigated the effects of bone marrow-derived progenitor cells (BMPCs) on the thrombin-induced endothelial permeability response. We observed that addition of BMPCs to endothelial monolayers at a fixed ratio prevented the thrombin-induced decrease in transendothelial electrical resistance, a measure of AJ integrity, and increased mouse pulmonary microvessel filtration coefficient, a measure of transvascular liquid permeability. The barrier protection was coupled to increased vascular endothelial cadherin expression and increased Cdc42 activity in ECs. Using small interfering RNA (siRNA) to deplete Cdc42 in ECs, we demonstrated a key role of Cdc42 in signaling the BMPC-induced endothelial barrier protection. Endothelial integrity induced by BMPCs was also secondary to inhibition of MLC phosphorylation in ECs. Thus BMPCs interacting with ECs prevent thrombin-induced endothelial hyperpermeability by a mechanism involving AJ barrier annealing, inhibition of MLC phosphorylation, and activation of Cdc42.

Original languageEnglish (US)
Pages (from-to)L36-L44
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1
StatePublished - Jan 2010


  • Adherens junctions
  • Cdc42
  • Myosin light chain
  • Vascular endothelial cadherin

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Pulmonary and Respiratory Medicine
  • Cell Biology


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