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Wickramasinghe, L.C.* ; Tsantikos, E.* ; Kindt, A.S.D.* ; Raftery, A.L.* ; Gottschalk, T.A.* ; Borger, J.G.* ; Malhotra, A.* ; Anderson, G.P.* ; van Wijngaarden, P.* ; Hilgendorff, A. ; Hibbs, M.L.*

Granulocyte colony-stimulating factor is a determinant of severe bronchopulmonary dysplasia and coincident retinopathy.

Am. J. Pathol. 193, 2001-2016 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Bronchopulmonary dysplasia (BPD), also called chronic lung disease of immaturity, afflicts approximately one third of all extremely premature infants, causing lifelong lung damage. There is no effective treatment other than supportive care. Retinopathy of prematurity (ROP), which impairs vision irreversibly, is common in BPD, suggesting a related pathogenesis. However, specific mechanisms of BPD and ROP are not known. Herein, a neonatal mouse hyperoxic model of coincident BPD and retinopathy was used to screen for candidate mediators, which revealed that granulocyte colony-stimulating factor (G-CSF), also known as colony-stimulating factor 3, was up-regulated significantly in mouse lung lavage fluid and plasma at postnatal day 14 in response to hyperoxia. Preterm infants with more severe BPD had increased plasma G-CSF. G-CSF-deficient neonatal pups showed significantly reduced alveolar simplification, normalized alveolar and airway resistance, and normalized weight gain compared with wild-type pups after hyperoxic lung injury. This was associated with a marked reduction in the intensity, and activation state, of neutrophilic and monocytic inflammation and its attendant oxidative stress response, and protection of lung endothelial cells. G-CSF deficiency also provided partial protection against ROP. The findings in this study implicate G-CSF as a pathogenic mediator of BPD and ROP, and suggest the therapeutic utility of targeting G-CSF biology to treat these conditions.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Bronchoalveolar Lavage Fluid; Chronic Lung-disease; Endothelial-cells; G-csf; Premature-infants; Hyperoxia; Oxygen; Increase; Model; Transdifferentiation
ISSN (print) / ISBN 0002-9440
e-ISSN 1525-2191
Journal American Journal of Pathology, The
Quellenangaben Volume: 193, Issue: 12, Pages: 2001-2016 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)
Grants German Center for Lung Research, German Ministry of Education and Health
International Research Group Role of BMP Signaling grant
German Ministry of Education and Health
Helm-holtz Foundation
Helmholtz Zentrum Muenchen, Germany
Helmholtz Foundation
Australian Government Research Training Program scholarship
Central Clinical School, Monash University
National Health and Medical Research Council, Australia