Differential activation of mixed venous and arterial neutrophils in patients with sepsis syndrome and acute lung injury

Neutrophil (PMN) functions, such as production of toxic oxygen (O₂) metabolites, adherence, and chemotactic properties, are modified during local tissue inflammation and sepsis. We hypothesized that PMN would be primed during their transit through injured tissue beds, which in turn can lead to modulation or retention of the primed PMN by downstream tissues like the lungs. We tested this hypothesis by measuring the transpulmonary gradient of hydrogen peroxide (H₂O₂) production by zymosan-activated PMN. We examined the mixed venous to arterial difference in H₂O₂(ΔH₂O₂) produced by zymosan-activated PMN in septic patients without lung infiltrates, patients with lung injury, and a control group of patients undergoing elective surgery or coronary catheterization. Septic patients had higher mixed venous H₂O₂/10⁶ PMN, whereas lung injury patients had higher arterial H₂O₂/10⁶ PMN. The control group had the same H₂O₂/10⁶ PMN in mixed venous and arterial blood. The ΔH₂O₂ in septic, lung injury, and control groups were 0.35 ± 0.22, -0.31 ± 0.48, and -0.01 ± 0.04 nmol H₂O₂/10⁶ PMN, respectively. The mixed venous to arterial H₂O₂ gradient distinguished septic patients from the control and lung injury patients (p < 0.05). Our results are consistent with the hypothesis that in septic patients PMN are primed in the periphery and downregulated or sequestered in the lung, and in lung injury patients PMN are primed in the lung and sequestered in the periphery. Alternatively, neutrophil-endothelial interactions may downregulate toxic O₂ metabolite production by PMN during their transit through microvascular beds.