G-CSF mediates lung injury in mice with adenine-induced acute kidney injury.

Authors :: Jing W
Qin F
Guo X
Sun Y
Yan C
Qiu C
Tanaka M
Shi B
Zhao Y
Source :: International immunopharmacology [Int Immunopharmacol] 2018 Oct; Vol. 63, pp. 1-8. Date of Electronic Publication: 2018 Jul 26.
Publication Year :: 2018
Abstract: Acute lung injury (ALI) is a serious complication among patients with acute kidney injury (AKI) that is a systemic inflammatory disease with high morbidity and mortality. The pathophysiology of AKI-associated ALI is poorly understood. G-CSF regulates the production and function of neutrophils that mediate lung injury via elastase and other mediators. Here, we used a mouse model of adenine-induced AKI to determine the roles of G-CSF and neutrophil elastase in AKI-associated ALI. We confirmed that ALI was associated with high serum G-CSF levels, and elevated neutrophil elastase activity in the lungs and serum of mice with adenine-induced AKI. Systemic administration of G-CSF-specific neutralizing antibody normalized granulopoiesis, pulmonary neutrophil infiltration, and neutrophil elastase activity, conferring improved lung architecture in mice with adenine-induced AKI. Further studies revealed that macrophages secreted G-CSF upon urea stimulation. Consequently, G-CSF could be a target for new anti-lung injury strategy in patients with AKI.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)