Neuraminidase alters red blood cells in sepsis

Objective: To investigate the influence of neuraminidase, an enzyme that cleaves sialic acid from the red blood cell (RBC) membrane, on RBC shape and biochemistry in critically ill patients. Design: Prospective, observational study and in vitro laboratory study. Setting: A 31-bed medico-surgical department of intensive care and a university-affiliated cell biology laboratory. Subjects: Acutely ill patients with and without sepsis and healthy volunteers. Interventions: Blood sampling in volunteers. Measurements and Main Results: Neuraminidase activity was measured using a fluorescent assay. RBC shape was assessed by the second coefficient of dissymmetry of Pearson using a flow cytometry technique at 25°C. Intraerythrocytic 2,3-diphosphoglycerate and lactate contents were also measured. Neuraminidase activity was significantly higher in septic patients compared with nonseptic patients and healthy volunteers (5.42 [4.85–6.00] vs. 4.53 [4.23–5.23] and 1.26 [0.83–1.83] mU/mL; all p < 0.05). Neuraminidase treatment modified the RBC shape in vitro in a dose–response fashion, and most of these alterations were present after 10 hours of incubation. Incubation of RBCs with phosphatidylinositol phospholipase C modified RBC shape and increased sialic acid concentrations in the supernatant, suggesting a leakage of neuraminidase from the RBC membrane. Alterations in shape were associated with increased 2,3-diphosphoglycerate (0.46 ± 0.25 vs. 0.19 ± 0.05 μmol/mL; p = 0.006) and lactate content (0.81 ± 0.07 vs. 0.66 ± 0.05 mmoL/L; p = 0.002). Conclusions: In sepsis, desialylation under the influence of increased neuraminidase activity may contribute to the alterations in RBC rheology. Inhibition of neuraminidase may represent a new therapeutic option to ameliorate RBC rheology and perhaps oxygen delivery to the cells.