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 language | English |
|---|---|
| Pages (from-to) | 651-661 |
| Number of pages | 11 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 57 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
Keywords
- Bleomycin
- CD34
- Influenza
- Lung injury
- Vascular endothelia
Cite this
}
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 journal › Article › Research › peer-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 -