Hypertonic saline attenuation of polymorphonuclear neutrophil cytotoxicity: Timing is everything

Background: The potential to modulate the inflammatory response has renewed interest in hypertonic saline (HTS) resuscitation of injured patients. However, the effect of the timing of HTS treatment with respect to polymorphonuclear neutrophil (PMN) priming and activation remains unexplored. We hypothesized that HTS attenuation of PMN functions requires HTS exposure before priming and activation. Methods: Isolated PMN were incubated in HTS (180 mM Na+) before L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF)/N-formylmethionyl-leucyl-phenylalanine (fMLP) priming/activation, after priming, or after priming/activation. Superoxide production was measured by the reduction cytochrome c, elastase release by cleavage of AAPV-pNA, and beta(2)-integrin expression by flow cytometry. Results: HTS before priming or activation decreased beta(2)-integrin expression, superoxide production, and elastase release. In contrast, HTS after priming/activation augmented superoxide production and elastase release. Conclusion: The timing of HTS is a key variable in the attenuation of PMN cytotoxic functions. Maximal attenuation of cytotoxicity is achieved before priming, whereas HTS exposure after activation augments cytotoxicity.