Loss of vascular CD34 results in increased sensitivity to lung injury

Bernard C. Lo, Matthew J. Gold, Sebastian Scheer, Michael R. Hughes, Jessica Cait, Erin Debruin, Fanny S.F. Chu, David C. Walker, Hesham Soliman, Fabio M. Rossi, Marie Renee Blanchet, Georgia Perona-Wright, Colby Zaph, Kelly M. McNagny

Research output: Contribution to journalArticleResearchpeer-review

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 Cd342/2 mice by bleomycin administration. We found that Cd342/2 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 Cd342/2mice reconstituted withWT hematopoietic cells exhibited early mortality compared with WT mice reconstituted with Cd342/2 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.

Original languageEnglish
Pages (from-to)651-661
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume57
Issue number6
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • Bleomycin
  • CD34
  • Influenza
  • Lung injury
  • Vascular endothelia

Cite this

Lo, Bernard C. ; Gold, Matthew J. ; Scheer, Sebastian ; Hughes, Michael R. ; Cait, Jessica ; Debruin, Erin ; Chu, Fanny S.F. ; Walker, David C. ; Soliman, Hesham ; Rossi, Fabio M. ; Blanchet, Marie Renee ; Perona-Wright, Georgia ; Zaph, Colby ; McNagny, Kelly M. / Loss of vascular CD34 results in increased sensitivity to lung injury. In: American Journal of Respiratory Cell and Molecular Biology. 2017 ; Vol. 57, No. 6. pp. 651-661.
@article{2674ff324b304903a9fc2d5ff9642272,
title = "Loss of vascular CD34 results in increased sensitivity to lung injury",
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 Cd342/2 mice by bleomycin administration. We found that Cd342/2 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 Cd342/2mice reconstituted withWT hematopoietic cells exhibited early mortality compared with WT mice reconstituted with Cd342/2 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 = "Bleomycin, CD34, Influenza, Lung injury, Vascular endothelia",
author = "Lo, {Bernard C.} and Gold, {Matthew J.} and Sebastian Scheer and Hughes, {Michael R.} and Jessica Cait and Erin Debruin and Chu, {Fanny S.F.} and Walker, {David C.} and Hesham Soliman and Rossi, {Fabio M.} and Blanchet, {Marie Renee} and Georgia Perona-Wright and Colby Zaph and McNagny, {Kelly M.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1165/rcmb.2016-0386OC",
language = "English",
volume = "57",
pages = "651--661",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "6",

}

Lo, BC, Gold, MJ, Scheer, S, Hughes, MR, Cait, J, Debruin, E, Chu, FSF, Walker, DC, Soliman, H, Rossi, FM, Blanchet, MR, Perona-Wright, G, Zaph, C & McNagny, KM 2017, 'Loss of vascular CD34 results in increased sensitivity to lung injury' American Journal of Respiratory Cell and Molecular Biology, vol. 57, no. 6, pp. 651-661. https://doi.org/10.1165/rcmb.2016-0386OC

Loss of vascular CD34 results in increased sensitivity to lung injury. / Lo, Bernard C.; Gold, Matthew J.; Scheer, Sebastian; Hughes, Michael R.; Cait, Jessica; Debruin, Erin; Chu, Fanny S.F.; Walker, David C.; Soliman, Hesham; Rossi, Fabio M.; Blanchet, Marie Renee; Perona-Wright, Georgia; Zaph, Colby; McNagny, Kelly M.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 57, No. 6, 01.12.2017, p. 651-661.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Loss of vascular CD34 results in increased sensitivity to lung injury

AU - Lo, Bernard C.

AU - Gold, Matthew J.

AU - Scheer, Sebastian

AU - Hughes, Michael R.

AU - Cait, Jessica

AU - Debruin, Erin

AU - Chu, Fanny S.F.

AU - Walker, David C.

AU - Soliman, Hesham

AU - Rossi, Fabio M.

AU - Blanchet, Marie Renee

AU - Perona-Wright, Georgia

AU - Zaph, Colby

AU - McNagny, Kelly M.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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 Cd342/2 mice by bleomycin administration. We found that Cd342/2 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 Cd342/2mice reconstituted withWT hematopoietic cells exhibited early mortality compared with WT mice reconstituted with Cd342/2 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.

AB - 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 Cd342/2 mice by bleomycin administration. We found that Cd342/2 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 Cd342/2mice reconstituted withWT hematopoietic cells exhibited early mortality compared with WT mice reconstituted with Cd342/2 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.

KW - Bleomycin

KW - CD34

KW - Influenza

KW - Lung injury

KW - Vascular endothelia

UR - http://www.scopus.com/inward/record.url?scp=85037117760&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2016-0386OC

DO - 10.1165/rcmb.2016-0386OC

M3 - Article

VL - 57

SP - 651

EP - 661

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 6

ER -