Platelet-rich plasma extract prevents pulmonary edema through angiopoietin-Tie2 signaling

Am J Respir Cell Mol Biol. 2015 Jan;52(1):56-64. doi: 10.1165/rcmb.2014-0076OC.


Increased vascular permeability contributes to life-threatening pathological conditions, such as acute respiratory distress syndrome. Current treatments for sepsis-induced pulmonary edema rely on low-tidal volume mechanical ventilation, fluid management, and pharmacological use of a single angiogenic or chemical factor with antipermeability activity. However, it is becoming clear that a combination of multiple angiogenic/chemical factors rather than a single factor is required for maintaining stable and functional blood vessels. We have demonstrated that mouse platelet-rich plasma (PRP) extract contains abundant angiopoietin (Ang) 1 and multiple other factors (e.g., platelet-derived growth factor), which potentially stabilize vascular integrity. Here, we show that PRP extract increases tyrosine phosphorylation levels of Tunica internal endothelial cell kinase (Tie2) and attenuates disruption of cell-cell junctional integrity induced by inflammatory cytokine in cultured human microvascular endothelial cells. Systemic injection of PRP extract also increases Tie2 phosphorylation in mouse lung and prevents endotoxin-induced pulmonary edema and the consequent decreases in lung compliance and exercise intolerance resulting from endotoxin challenge. Soluble Tie2 receptor, which inhibits Ang-Tie2 signaling, suppresses the ability of PRP extract to inhibit pulmonary edema in mouse lung. These results suggest that PRP extract prevents endotoxin-induced pulmonary edema mainly through Ang-Tie2 signaling, and PRP extract could be a potential therapeutic strategy for sepsis-induced pulmonary edema and various lung diseases caused by abnormal vascular permeability.

Keywords: Tunica internal endothelial cell kinase; angiopoietin; lung; platelet-rich plasma extract; vascular permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiopoietin-1 / metabolism*
  • Animals
  • Blood Component Transfusion*
  • Capillary Permeability / drug effects
  • Endotoxins / toxicity
  • Humans
  • Mice
  • Phosphorylation
  • Plasma*
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / metabolism
  • Pulmonary Edema / pathology
  • Pulmonary Edema / prevention & control*
  • Receptor, TIE-2 / metabolism*
  • Sepsis / complications
  • Sepsis / metabolism
  • Sepsis / pathology
  • Signal Transduction / drug effects*


  • Angiopoietin-1
  • Angpt1 protein, mouse
  • Endotoxins
  • Receptor, TIE-2
  • Tek protein, mouse