Hypertonic Saline Inhibits Arachidonic Acid Priming of the Human Neutrophil Oxidase

Abstract

Background Arachidonic acid (AA, and its leukotriene derivatives e.g.: LTB4) is an inflammatory mediator in post-shock mesenteric lymph that appears to act as an agonist on G-protein coupled receptors (GPCRs). These mediators prime neutrophils (PMNs) for an increased production of superoxide, implicated in the development of ALI. Hypertonic saline (HTS) has also been shown to have immunomodulatory effects such as attenuation of PMN priming by precluding appropriate clathrin-mediated endocytosis of activated GPCRs, thereby potentially attenuating ALI. We hypothesize that HTS inhibits priming of the PMN oxidase by these lipid mediators. Methods After PMNs were isolated from healthy donors, incubation was done in either isotonic buffer (control) or HTS (180 mmol/L) for 5 minutes at 37°C. The PMNs were then primed for 10 minutes with AA [5 μM] or 5 minutes with LTB4 [1 μM] and the oxidase was activated with 200 ng/ml of phorbol 12-myristate 13-acetate (PMA), a non-GPCR activator, and superoxide anion generation was measured via reduction of cytochrome c. Results Both AA [5 μM] and LTB4 [1 μM] significantly primed the PMA activated respiratory burst (p<0.05, ANOVA, Newman-Keuls, n=4). HTS inhibited both AA and LTB4 priming of the respiratory burst. Conclusions These data indicate that HTS reduces the cytotoxicity of PMNs stimulated by these lipid mediators in vitro and further support the immunomodulatory effects of HTS.

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Dissociation of Inflammatory Mediators and Function

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