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- Title
Bone Marrow-Derived Endothelial Progenitor Cells Strengthen the Endothelial Barrier by a Rac1/Cdc42-Mediated Adherens Junction Assembly.
- Authors
Zhao, Yidan; Ohkawara, Hiroshi; Malik, Asrar
- Abstract
We addressed the possibility that endothelial progenitor cells (EPCs) promote annealing of the endothelial barrier, preventing the increase in lung microvascular permeability and edema formation those results from LPS challenge and additionally the mechanisms of this EPC-mediated endothelial barrier protection. Flk1- and CD34-positive EPCs were injected intravenously (i.v.) into mice which were then challenged intraperitoneally (i.p.) with LPS. We observed that 83% of EPC-transplanted mice survived the 3 d period after LPS (15 mg/kg) whereas survival of control mice was only 11%. EPCs prevented the LPS-induced increase in the pulmonary microvessel filtration coefficient (a measure of vessel wall permeability) and pulmonary edema. Injection of endothelial cells (ECs) in control experiments had no protective effect. EPCs added in increasing numbers to confluent EC monolayers in vitro increased transendothelial electrical resistance (TER), a measure of endothelial junctional integrity. EPCs also increased membrane-association of VE-cadherin and this was dependent on the activation of the RhoGTPases Rac1 and Cdc42. The observed endothelial barrier protection induced by EPCs was secondary to release of paracrine mediators from the EPCs that did not require EPC/EC contact. Thus, EPC transplantation strengthens the endothelial barrier and prevents the sepsis-induced increase in lung microvascular permeability and edema formation by activating Rac1- and Cdc42-mediated adherens junction assembly. These findings raise the possibility of EPC-based therapy for re-annealing the lung microvascular endothelial barrier in ALI patients.
- Publication
FASEB Journal, 2008, Vol 22, p660
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.22.2_supplement.660