HYPERTONIC SALINE ACTIVATES LIPID-PRIMED HUMAN NEUTROPHILS FOR ENHANCED ELASTASE RELEASE

Background: Ongoing clinical trials have revived interest in hypertoni c saline (HTS) for postinjury resuscitation; these studies have docume nted serum Na+ concentrations greater than or equal to 170 mmol/L. Rec ent animal studies have shown that HTS enhances T-cell and monocyte fu nction, but effects on the polymorphonuclear neutrophil (PMN) remain u nclear. The postinjury lipid mediators platelet-activating factor (PAF ) and leukotriene B-4 (LTB4) have been implicated in PMN priming for c ytotoxicity, which is believed to be important in PMN priming for cyto toxicity, which is believed to be important in the pathogenesis of mul tiple organ failure. We hypothesized that HTS would stimulate PMN supe roxide (O-2(-)) and elastase release from PAF- and LTB4-primed PMNs. M ethods: Isolated PMNs from five donors were primed for 5 minutes with 200 nmol/L PAF or 1 mu mol/L LTB4 in Kreb's-Ringer's phosphate with de xtrose at a Na+ concentration of 140 mmol/L (normal serum Na+ concentr ation), pelleted, and resuspended in Kreb's-Ringer's phosphate with de xtrose for 10 minutes at a Na+ concentration of 130 to 170 mmol/L. O-2 (-) generation was measured by superoxide dismutase-inhibitable reduct ion of cytochrome c and elastase release by cleavage of N-methoxysucci nyl-Ala-Ala-Pro-Val p-nitroanilide. Results: HTS with Na+ concentratio n up to 170 mmol/L had no significant effect on O-2(-) production or e lastase release from quiescent cells. Na+ concentration of 160 and 170 mmol/L, however, activated PAF- and LTB4-primed PMNs for enhanced ela stase release with no effect on O-2(-) production. Conclusion: In clin ically relevant concentrations, elevated Na+ activates lipid-primed ne utrophils for enhanced elastase degranulation. Consequently, the admin istration of HTS in the early postinjury resuscitation period, when PM Ns are maximally primed, may activate PMN elastase release and thereby promote the development of multiple organ failure.