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Revista Medicina - HIGH SALT BUT NOT HYPEROSMOLARITY INDUCES A DELAYED ACTIVATION PATTERN IN HUMAN NEUTROPHILS

Congreso

Autoría
Ignacio Mazzitelli ; BLEICHMAR, LUCIA ; Fernando Erra Díaz ; Claudia Melucci ; Jorge Geffner
Fecha
2022
Editorial y Lugar de Edición
Medicina
Resumen Información suministrada por el agente en SIGEVA
Elevated concentrations of salt (NaCl) are present in a number of tissuesunder physiological and pathological conditions. We have previouslyreported a paradoxical time-dependant effect of high NaCl(50 mM) on neutrophil function: an early paralysis followed by adelayed stimulation of neutrophil responses, such as IL-8 and ROSproduction. Here, we analyzed whether the effect induced by NaClon neutrophil function was related to a direct action exerted by NaClor to osmotic stress. Neutrophils were i... Elevated concentrations of salt (NaCl) are present in a number of tissuesunder physiological and pathological conditions. We have previouslyreported a paradoxical time-dependant effect of high NaCl(50 mM) on neutrophil function: an early paralysis followed by adelayed stimulation of neutrophil responses, such as IL-8 and ROSproduction. Here, we analyzed whether the effect induced by NaClon neutrophil function was related to a direct action exerted by NaClor to osmotic stress. Neutrophils were isolated from human blood byconventional procedures (purity >95%). Increasing osmolarity of theculture medium by the addition of sorbitol or mannitol (100 mM) wascompletely unable to stimulate neutrophil responses, suggestingthat high sodium but not an increased osmolarity mediates the activationon neutrophil responses: production of IL-8 at 8 h of culturewas 0±0, 4102±384, 0±0 and 0±0 (pg/ml), for neutrophils culturedin control medium or in the presence of medium supplemented withNaCl (50 mM), manitol (100 mM), or sorbitol (100 mM) (p<0.001 forNaCl 50 mM vs other conditions, N=3). Similarly, production of ROSevaluated by DHR oxidation and flow cytometry revealed that highNaCl, but neither sorbitol nor manitol, increased ROS production(not shown). By contrast, the early (< 2 hs) inhibition of IL-8 production mediated by LPS stimulation was inhibited more than 95% (n=6)by NaCl (50 mM), manitol or sorbitol (100 mM). Surprisingly, earlyROS production induced by fMLP was unaffected by sorbitol andmannitol, but strongly inhibited by NaCl 50 mM (% inhibition > 50,n=8). Interestingly we also observed that while phagocytosis of unopsonized-C. albicans was significantly inhibited by high salt (>72%,p<0.01, n=4), no inhibition was observed when opsonized yeastwere used (not shown). Our results shed light about the complexmechanisms through which high salt modulates neutrophil function.
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Palabras Clave
NeutrophilsHigh Salt