Intestinal epithelial cells modulate PMN activation and apoptosis following bacterial and hypoxic challenges

Background. The post-ischemic gut may serve to prime and activate neutrophils which may lead to the subsequent development of the systemic inflammatory response syndrome (SIRS) and multiple organ failure. However, the initiating event which may trigger this immunoinflammatory cascade from the gut is unknown. Recent studies have indicated that intestinal epithelial cells (IEC) play an integral role in generating and transmitting signals between luminal bacteria and the host cells in the underlying gut tissues. The purpose of this study was to investigate the ability of IEC to modulate PMN responses to bacteria and/or hypoxia/reoxygenation (H/R) challenges in vitro. Method: Caco2 cell monolayers were established in a two-chamber cell culture system. Neutrophils from normal human volunteers were placed in the basal chamber and the cell co-culture exposed to either apical bacteria (E. coli) and/or H/R challenge. PMN apoptosis, and percentage of CD11b expression, superoxide anion production, and elastase release were subsequently quantitated. Results: Coculture of PMNs with Caco2 cells led to a significant reduction in neutrophil apoptosis in both normoxic and H/R conditions. CD11b expression was increased in PMNs exposed to bacteria but the greatest expression was noted with PMN cocultured with Caco2 cells and H/R. Superoxide anion production was increased in all groups following either H/R or bacterial challenge and H/R. Elastase release was highest in neutrophils following H/R and exposure to E. coli. Conclusion: IEC modulate PMN response to bacteria and H/R insults. This results in the production of activated neutrophils with an exaggerated lifespan which may promote remote organ failure. Attempts to modulate this response may be useful in preventing multiple organ failure following severe traumatic shock.