BACKGROUND: Arachidonic acid (AA, and its leukotriene derivatives, e.g., LTB(4)) 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 acute lung injury (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 min at 37°C. The PMNs were then primed for 10 min with AA [5 μM] or 5 min with LTB(4) [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 LTB(4) [1 μM] significantly primed the PMA activated respiratory burst (P < 0.05, ANOVA, Newman-Keuls, n = 4). HTS inhibited both AA and LTB(4) 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.
BACKGROUND:Arachidonic acid (AA, and its leukotriene derivatives, e.g., LTB(4)) 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 acute lung injury (ALI). Hypertonicsaline (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 min at 37°C. The PMNs were then primed for 10 min with AA [5 μM] or 5 min with LTB(4) [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 LTB(4) [1 μM] significantly primed the PMA activated respiratory burst (P < 0.05, ANOVA, Newman-Keuls, n = 4). HTS inhibited both AA and LTB(4) 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.
Authors: Ernest E Moore; Frederick A Moore; Alden H Harken; Jeffrey L Johnson; David Ciesla; Ani Banerjee Journal: Shock Date: 2005-12 Impact factor: 3.454
Authors: Sandro B Rizoli; Shawn G Rhind; Pang N Shek; Kenji Inaba; Dennis Filips; Homer Tien; Fred Brenneman; Ori Rotstein Journal: Ann Surg Date: 2006-01 Impact factor: 12.969
Authors: Phillip C Eckels; Anirban Banerjee; Ernest E Moore; Nathan J D McLaughlin; Lynn M Gries; Marguerite R Kelher; Kelly M England; Fabia Gamboni-Robertson; Samina Y Khan; Christopher C Silliman Journal: Am J Physiol Cell Physiol Date: 2009-03-18 Impact factor: 4.249
Authors: Janeen R Jordan; Ernest E Moore; Eric L Sarin; Sagar S Damle; Sara B Kashuk; Christopher C Silliman; Anirban Banerjee Journal: J Appl Physiol (1985) Date: 2008-02-14