G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema, and hypoxia

Christian Hierholzer, Edward Kelly, Valerie Lyons, Eva Roedling, Paul Davies, Timothy R. Billiar, David J. Tweardy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Activated neutrophils (PMN) have been implicated in the pathogenesis of adult respiratory distress syndrome (ARDS). Granulocyte colony-stimulating factor (G-CSF) is essential for PMN production and activation of PMN functions. We have recently shown that levels of G-CSF mRNA in a rat model of hemorrhagic shock correlated with severity of shock, PMN infiltration, pulmonary edema, and hypoxia. To determine whether increased tissue levels of G-CSF contribute to PMN recruitment and PMN-mediated injury, we instilled G- CSF into the lungs by intratracheal injection. Animals treated with G-CSF became hypoxic, hypocapnic, and alkalotic and demonstrated increased BAL fluid cellularity compared with control animals. The wet-to-dry ratio increased significantly after G-CSF instillation and peaked at 12 h. Histological examination of the lungs from G-CSF-treated rats revealed marked edema and increased PMN within the interstitium and alveoli. These results indicate that the presence of G-CSF alone in the lung can lead to recruitment of PMN, lung injury, and impaired pulmonary function, suggesting that local production of G-CSF may contribute to the development of lung damage and possibly ARDS in the setting of resuscitated hemorrhagic shock.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalJournal of Leukocyte Biology
Issue number2
StatePublished - Feb 1998
Externally publishedYes


  • Cytokines
  • In vivo animal model
  • Inflammation


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