Document Detail


Neutrophils from pregnant women produce thromboxane and tumor necrosis factor-alpha in response to linoleic acid and oxidative stress.
MedLine Citation:
PMID:  16150282     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Preeclampsia is associated with oxidative stress, neutrophil activation, neutrophil infiltration into systemic vasculature, and elevated plasma levels of linoleic acid, the fatty acid precursor to arachidonic acid and its metabolite, thromboxane. In this study we evaluated whether linoleic acid under conditions of oxidative stress would stimulate neutrophil production of thromboxane and tumor necrosis factor-alpha. STUDY DESIGN: Neutrophils were isolated from 14 normal pregnant women. Western blot demonstrated cyclooxygenase-2 expression at 18 hours of incubation, so this incubation time was used for experiments. Neutrophils (2 x 10(6) cells/mL) were incubated in Dulbecco's modified Eagle's medium/F-12 with: (1) linoleic acid control; (2) an oxidizing solution enriched with linoleic acid; (3) oxidizing solution enriched with linoleic acid plus indomethacin; (4) oxidizing solution enriched with linoleic acid plus aspirin; (5) oxidizing solution enriched with linoleic acid plus NS-398, a specific inhibitor of cyclooxygenase-2; or (6) oxidizing solution enriched with linoleic acid plus pinane thromboxane, a thromboxane synthase inhibitor and receptor blocker. RESULTS: Oxidizing solution enriched with linoleic acid significantly increased oxidative stress in neutrophils. Compared with linoleic acid, oxidizing solution enriched with linoleic acid significantly increased neutrophil production of thromboxane and tumor necrosis factor-alpha. Indomethacin and aspirin inhibited oxidizing solution enriched with linoleic acid stimulation of thromboxane, but NS-398 was equally effective implicating cyclooxygenase-2 in the thromboxane response. Indomethacin inhibited oxidizing solution enriched with linoleic acid stimulation of tumor necrosis factor-alpha, but so did pinane thromboxane implicating thromboxane in the tumor necrosis factor-alpha response. CONCLUSIONS: These data demonstrate that exposure of neutrophils from normal pregnant women to conditions present in preeclamptic women results in neutrophil activation with release of thromboxane and tumor necrosis factor-alpha. Newly synthesized thromboxane is cyclooxygenase-2 dependent and plays a role in the tumor necrosis factor-alpha response. Our data suggest a mechanism for maternal vasoconstriction and vascular inflammation in preeclampsia because activated, thromboxane-secreting neutrophils migrate across endothelium into the microenvironment of the vasculature in which they could promote vasoconstriction, whereas release of tumor necrosis factor-alpha could cause vascular inflammation.
Authors:
John E Vaughan; Scott W Walsh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  193     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-09     Completed Date:  2005-10-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  830-5     Citation Subset:  AIM; IM    
Affiliation:
Departments of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Female
Humans
Linoleic Acid / pharmacology*
Lipid Peroxides / analysis
Neutrophils / metabolism*
Oxidative Stress / physiology*
Pregnancy
Thromboxanes / metabolism*
Tumor Necrosis Factor-alpha / metabolism*
Grant Support
ID/Acronym/Agency:
HD 20973/HD/NICHD NIH HHS; HL069851/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipid Peroxides; 0/Thromboxanes; 0/Tumor Necrosis Factor-alpha; 2197-37-7/Linoleic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine releas...
Next Document:  Heat shock protein-70 and 4-hydroxy-2-nonenal adducts in human placental villous tissue of normotens...