Granulocyte colony-stimulating factor (G-CSF) production and neutrophil activation in hemorrhagic shock

Hemorrhagic shock (HS) initiates a series of inflammatory processes that contribute to organ injury and dysfunction, which includes the activation of polymorphonuclear cells (PMN) at critical sites such as the liver and the lung. G-CSF activates PMN via a signaling cascade that includes a distinct member of the signal transducers and activators of transcription (STAT) protein family: StatG. Sprague-Dawley rats were subjected to mild or severe HS (MAP 40 mm Hg) followed by resuscitation times ranging from 4 to 8 hours. At the 4 hour time point mild and severe HS groups showed statistically significant differences in levels of G-CSF expression between shock and sham animals as determined by semiquantitative PCR in all organs studied. However, by 8 hours the differences in G-CSF mRNA levels occured only in the severe shock groups. G-CSF expression is enhanced in the lung, liver and gut following HS. Critical parameters are duration and severity of shock. Examination of StatG activation in circulating neutrophils demonstrated activation in 9 of 10 shock animals versus only 5 of 10 sham animals. PMN traversing the circulation of these tissues bind G-CSF and become activated as determined by StatG activation. Thus, increased local G-CSF levels may contribute to PMN recruitment and activation in HS.