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Type: Journal article
Title: Local delivery of GM-CSF protects mice from lethal pneumococcal pneumonia
Author: Steinwede, K.
Tempelhof, O.
Bolte, K.
Maus, R.
Bohling, J.
Ueberberg, B.
Langer, F.
Christman, J.
Paton, J.
Ask, K.
Maharaj, S.
Kolb, M.
Gauldie, J.
Welte, T.
Maus, U.
Citation: Journal of Immunology, 2011; 187(10):5346-5356
Publisher: Amer Assoc Immunologists
Issue Date: 2011
ISSN: 0022-1767
Statement of
Kathrin Steinwede, Ole Tempelhof, Kristine Bolte, Regina Maus, Jennifer Bohling, Bianca Ueberberg, Florian Länger, John W. Christman, James C. Paton, Kjetil Ask, Shyam Maharaj, Martin Kolb, Jack Gauldie, Tobias Welte and Ulrich A. Maus
Abstract: The growth factor GM-CSF has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities of lung sentinel cells. However, the potential of intra-alveolar GM-CSF to augment lung protective immunity against inhaled bacterial pathogens has not been defined in preclinical infection models. We hypothesized that transient overexpression of GM-CSF in the lungs of mice by adenoviral gene transfer (Ad-GM-CSF) would protect mice from subsequent lethal pneumococcal pneumonia. Our data show that intra-alveolar delivery of Ad-GM-CSF led to sustained increased pSTAT5 expression and PU.1 protein expression in alveolar macrophages during a 28-d observation period. Pulmonary Ad-GM-CSF delivery 2–4 wk prior to infection of mice with Streptococcus pneumoniae significantly reduced mortality rates relative to control vector-treated mice. This increased survival was accompanied by increased inducible NO synthase expression, antibacterial activity, and a significant reduction in caspase-3–dependent apoptosis and secondary necrosis of lung sentinel cells. Importantly, therapeutic treatment of mice with rGM-CSF improved lung protective immunity and accelerated bacterial clearance after pneumococcal challenge. We conclude that prophylactic delivery of GM-CSF triggers long-lasting immunostimulatory effects in the lung in vivo and rescues mice from lethal pneumococcal pneumonia by improving antibacterial immunity. These data support use of novel antibiotic-independent immunostimulatory therapies to protect patients against bacterial pneumonias.
Keywords: Lung
Bronchoalveolar Lavage Fluid
Mice, Inbred C57BL
Pneumonia, Pneumococcal
Granulocyte-Macrophage Colony-Stimulating Factor
Recombinant Proteins
Gene Transfer Techniques
Intubation, Intratracheal
Genetic Vectors
Rights: Copyright 2011 by The American Association of Immunologists, Inc.
DOI: 10.4049/jimmunol.1101413
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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