Neutrophil Extracellular Traps (NETs) in Septic and Burn Patients

MAGOSEVICH D; D'ATRI LP; FONDEVILA C; MORENO C; CARESTIA A; SCHATTNER M; KAUFMAN T; GUZMAN A; PALIZAS F

Congreso; XXVI Congress of the International Society on Thrombosis and Haemostasis; 2017

Background: NET formation (NETosis) is a mechanism of host defenseagainst microbes associated with tissue damage. Besides pathogens,NETs are triggered by mediators of sterile inflammation and activatedplatelets.Aims: We determined the presence of NETs in septic and burn patientsand correlated them with organ damage, patient evolution,platelet activation and pro-inflammatory cytokines.Methods: 25 septic and 23 burn patients were studied at 1 and 4 dayspost admission (dpa) to the intensive care unit and 30 healthy donorsas control. Plasmatic nucleosomes and Human Neutrophil Elastase(HNE)-DNA complexes were measured as indirect and direct NETosisindicators, respectively (ELISA). Ex vivo NETosis was studied by DNArelease (fluorometry); platelet P-selectin and toll like receptor 4 (TLR4)by cytometry and IL6 and TNFα by ELISA.Results: Plasmatic nucleosomes and HNE-DNA complexes were elevatedin septic and burn patients at 1 dpa remaining high at 4 dpaand a positive correlation between them was found in septic but not inburn patients. Nucleosomes from septics correlated with SOFA score at 1 dpa (p< 0.05) and were significantly associated with mortalitywithin 30 dpa (p< 0.05, logistic reg.)Spontaneous DNA release was elevated in neutrophils from septics andwhile their stimulation with platelets+LPS or TNFα triggered DNA releasein the control group, neutrophils from septic or burn did not respond.While P-selectin exposure was increased in both patients groupsthrough the study, higher platelet TLR4 expression was found in septicsat 1 dpa.TNFα levels were elevated in septic and burn patients. IL6 levels werehigh in both groups at 1dpa and decreased in septics by 4dpa. Neitherplatelet activation markers nor cytokine levels correlated with nucleosomesor HNE-DNA.Conclusions: Nucleosomes could be an organ damage indicator andpredictor of mortality in septic but not in burn patients. Platelet activationand pro-inflammatory cytokines appear not be key mediatorsof NETosis in these groups of patients.