Loss of Vascular CD34 Results in Increased Sensitivity to Lung Injury
| Autor: | Jessica Cait, Matthew J. Gold, Michael R. Hughes, Fanny Chu, Georgia Perona-Wright, David C. Walker, Hesham Soliman, Fabio M.V. Rossi, Marie Renee Blanchet, Kelly M. McNagny, Colby Zaph, Bernard C. Lo, Erin J. DeBruin, Sebastian Scheer |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Stromal cell Angiogenesis Clinical Biochemistry Cell CD34 Antigens CD34 Pulmonary Edema Biology Lung injury Bleomycin 03 medical and health sciences chemistry.chemical_compound Mice medicine Animals Cell adhesion Molecular Biology Mice Knockout Lung Cell Biology Lung Injury 030104 developmental biology medicine.anatomical_structure chemistry Airway Remodeling Endothelium Vascular |
| Zdroj: | American journal of respiratory cell and molecular biology. 57(6) |
| ISSN: | 1535-4989 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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