Increased neutrophil migration rescues impaired function and susceptibility to Pseudomonas pneumonia after burn injury (56.25)

Abstract

Abstract Bacterial lung infection is a major cause of mortality late after burn injury. Neutrophil dysfunction is implicated in the susceptibility of wound infection with Pseudomonas aeruginosa. We hypothesized that burn-induced impaired neutrophil migration and function within the lungs would increase susceptibility to intratracheal P. aeruginosa infection. Female C57BL/6 mice were anesthetized and subjected to a 20% full thickness contact burn or sham injury. Fourteen days later, mice were inoculated with 1x106 CFU of P. aeruginosa. After 24 hours, pulmonary bacterial load was evaluated. Flow cytometric analysis was used to quantify neutrophils and evaluate their function by dihydrorhodamine (DHR) oxidation. Contrary to our hypothesis, burn mice had a significant increase in bacterial clearance compared to sham. This correlated with an increased percentage and absolute number of lung neutrophils in burn mice (mean±SEM, burn: 2.5±1.4x108, sham: 2.7±0.8x107cells, p=0.007). However, these neutrophils had reduced reactive-oxygen production compared to sham (burn: 1044±21, sham: 51431±182 MFI of oxidized DHR, p=0.0131). As predicted, lung neutrophil function was significantly impaired after burn injury. However, burn mice exhibited a larger neutrophil influx than sham. The net result was that burn mice cleared the infection quicker than sham mice. This implies a fine balance exists between neutrophil migration and function after burn injury.