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Endothelial EphA receptor stimulation increases lung vascular permeability

Developmental Lung Biology Laboratory and Section of Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado

Submitted 1 April 2008 ; accepted in final form 30 June 2008

Mediators of angiogenesis such as VEGFs and angiopoietins may regulate pulmonary vascular permeability under normal and pathological conditions. Ephrin family receptor tyrosine kinases are expressed in the vasculature and also regulate angiogenesis under some circumstances, but whether they also modulate lung vascular permeability is unknown. We hypothesized that stimulation of lung endothelial EphA receptors with ephrin-a1 ligand would alter pulmonary vascular permeability and tested this idea in vivo and in vitro. We found that ephrin-a1 ligand and EphA2 receptors are expressed in distal normal lung vasculature and that their expression is increased in injured lung, suggesting a link to mechanisms of increased permeability. Intravenous injection of ephrin-a1 caused a large increase in the leakage of labeled albumin into the lungs of rats within 30 min (293 ± 27 vs. 150 ± 6 ng/mg dry lung, P < 0.01), along with histological evidence of the formation of endothelial disruptions. In cultured lung vascular endothelial cells, stimulation with ephrin-a1 increased monolayer permeability by 44% (P < 0.01), a permeability change similar to that seen with VEGF stimulation of the same cells. Ephrin-a1 stimulation in vivo and in vitro was associated with histological evidence for disruptions of tight and adherens junctions. These observations describe a novel role for ephrin-a1 and EphA receptors in the regulation of vascular permeability in the lung.

ephrin; EphA2; pulmonary edema

This article has been cited by other articles:

				M. A. Cercone, W. Schroeder, S. Schomberg, and T. C. Carpenter EphA2 receptor mediates increased vascular permeability in lung injury due to viral infection and hypoxia Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L856 - L863. [Abstract] [Full Text] [PDF]