Loss of vascular CD34 results in increased sensitivity to lung injury

Lo, B. C. et al. (2017) Loss of vascular CD34 results in increased sensitivity to lung injury. American Journal of Respiratory Cell and Molecular Biology, 57(6), pp. 651-661. (doi: 10.1165/rcmb.2016-0386OC) (PMID:28683207)

[img]
Preview
Text
142355.pdf - Accepted Version

9MB

Abstract

Survival during lung injury requires a coordinated program of damage limitation and rapid repair. CD34 is a cell surface sialomucin expressed by epithelial, vascular and stromal cells that promotes cell adhesion, coordinates inflammatory cell recruitment, and drives angiogenesis. To test whether CD34 also orchestrates pulmonary damage and repair, we induced acute lung injury in wild type (WT) and Cd34-/- mice by bleomycin (BLM) administration. We found that Cd34-/- mice displayed severe weight loss and early mortality compared to WT controls. Despite equivalent early airway inflammation to WT mice, CD34-deficient animals developed interstitial edema and endothelial delamination, suggesting impaired endothelial function. Chimeric Cd34-/- mice reconstituted with WT hematopoietic cells exhibited early mortality compared to WT mice reconstituted with Cd34-/- cells, supporting an endothelial defect. CD34-deficient mice were also more sensitive to lung damage caused by influenza infection, showing greater weight loss and more extensive pulmonary remodeling. Together our data suggest that CD34 plays an essential role in maintaining vascular integrity in the lung in response to chemical- and infection-induced, tissue damage.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Perona-Wright, Dr Georgia
Authors: Lo, B. C., Gold, M. J., Scheer, S., Hughes, M. R., Cait, J., Debruin, E., Chu, F. S.F., Walker, D. C., Soliman, H., Rossi, F. M., Blanchet, M.-R., Perona-Wright, G., Zaph, C., and McNagny, K.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:American Journal of Respiratory Cell and Molecular Biology
Publisher:American Thoracic Society
ISSN:1044-1549
ISSN (Online):1535-4989
Published Online:06 July 2017
Copyright Holders:Copyright © 2017 American Thoracic Society
First Published:First published in American Journal of Respiratory Cell and Molecular Biology 2017
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record