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Am J Respir Cell Mol Biol. 2017 Dec;57(6):651-661. doi: 10.1165/rcmb.2016-0386OC.

Loss of Vascular CD34 Results in Increased Sensitivity to Lung Injury.

Author information

1
1 The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
2
2 Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
3
3 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
4
4 Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec, Canada.
5
5 Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; and.
6
6 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.

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 administration. We found that Cd34-/- mice displayed severe weight loss and early mortality compared with 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 with 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.

KEYWORDS:

CD34; bleomycin; influenza; lung injury; vascular endothelia

PMID:
28683207
DOI:
10.1165/rcmb.2016-0386OC
[Indexed for MEDLINE]

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