Hypertonic saline activation of P38 MAPK primes the PMN respiratory burst

investigation of hypertonic saline (HTS) modulation of neutrophils (PMN) cy totoxic responses has generated seemingly contradictory results. Clinically relevant levels of HTS attenuate receptor-mediated p38 MAPK signaling, whe reas higher levels activate p38 MAPK. Concurrently, HTS exerts a dose-depen dent attenuation of the PMN respiratory burst, most notably at concentratio ns where p38 MAPK is activated. We hypothesized that HTS-mediated p38 MAPK activation augments the PMN respiratory burst on return to normotonicity. W e found that although clinically relevant levels of HTS (Na+ greater than o r equal to 200 mM) did not activate p38 MAPK, higher concentrations (Na+ gr eater than or equal to 300 mM) resulted in activation comparable with that after PAF stimulation. Transient stimulation with high levels of HTS primed the PMN respiratory burst in response to fMLP and PMA. This effect was att enuated by pretreatment with SB 203580, a p38 MAPK specific inhibitor. We c onclude that severe osmotic shock primes the respiratory burst via p38 MAPK signaling, further supporting the role of this signaling cascade in PMN pr iming.