Tyrosine Nitration of Plasma Proteins and Polymorphonuclear Cells in the Progression of Human Sepsis

CARRERAS MC; RIOBÓ N; CONVERSO D; BAREDES N; DEL BOSCO G; PODEROSO JJ

San Francisco, EEUU

Congreso; First International Conference Biology, Chemistry ad Therapeutic Applications of Nitric Oxide.; 2000

NO Society

Sepsis is a generalized inflammatory response partially dependent on nitric oxide and derived products. Accordingly, peroxynitrite overproduction, evidence as tyrosine nitration, has recently been associated to cellular and organ dysfunction in children with sepsis- induced lung injury. The aim of this study was to evaluate plasma and neutrophil protein nitration as humoral markers of the progression and severity of organ failure. Patients were categorized according to the severity of the inflammatory/septic response. The study included three groups of patients: a) healthy control (n=25), b) patients with mild systemic inflammatory response syndrome (SIRS) (n=10) and c) patients with multiple organ dysfunction (MODS) (n=15). Plasma No metabolites (Nox) were significantly increased in MODS group (23±5 ìM*) but not in SIRS patients (7±2ìM) when compared to control (8±2 ìM) (*p<0.05); and correlated with APACHE II clinical score (r= 0.634, p<0.05). In addition, tyrosine nitration of plasma and circulating neutrophils became more evident with the progression of sepsis; and thus, it was slightly detected in SIRS patients but marked in the MODS group. Interestingly, an overexpressionof neutrophil neuronal NO synthase was observed in septic patients respect to control, which was associated with increased tyrosine nitration. . We conclude that an increase in protein tyrosine nitration, both in plasma proteins and circulating leukocytes of severely ill patients, confirms the participation of the underlying mechanism in the onset of organ dysfunction and indicates the clinical progression of sepsis.