GRANULOCYTE-COLONY-STIMULATING FACTOR (G- CSF) PRODUCTION AND NEUTROPHIL ACTIVATION IN HEMORRHAGIC-SHOCK

Hemorrhagic shock (HS) initiates a series of inflammatory processes th at contribute to organ injury and dysfunction, which includes the acti vation of polymorphonuclear cells (PMN) at critical sites such as the liver and the lung. G-CSF activates PMN via a signaling cascade that i ncludes a distinct member of the signal transducers and activators of transcription (STAT) protein family: StatG. Sprague-Dawley rats were s ubjected 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 se vere HS groups showed statistically significant differences in levels of G-CSF expression between shock and sham animals as determined by se miquantitative PCR in all organs studied. However, by 8 hours the diff erences 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 i n 9 of 10 shock animals versus only 5 of 10 sham animals. PMN traversi ng the circulation of these tissues bind G-CSF and become activated as determined by StatG activation. Thus, increased local G-CSF levels ma y contribute to PMN recruitment and activation in HS.