Docosahexanoic acid (22:6, n-3) but not eicosapentaenoic acid (20:5, n-3) can induce neutrophil-mediated injury of cultured endothelial cells: Involvement of neutrophil elastase

E. J. Bates, A. Ferrante, D. P. Harvey, M. Nandoskar, A. Poulos

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30 Citations (Scopus)


Previously published work has indicated that polyunsaturated fatty acids (PUFA) may enhance neutrophil-mediated damage to host tissues. We have found that endothelial detachment was significantly increased by neutrophils pretreated with docosahexanoic (22:6, n-3) and arachidonic (20:4, n-6) acids at 10-40 μM but not by eicosapentaenoic acid (20:5, n-3). Endothelial cell lysis as measured by 51Cr release was unaffected. The extent of detachment was dependent on both fatty acid and neutrophil pretreatment concentrations. A specific leukocyte elastase inhibitor abrogated the increased detachment but catalase had no effect. Measurement of prostaglandin I2 synthesis as an alternative nonlytic assay of endothelial function indicated that 20:4 but not 20:5 was able to stimulate neutrophil-induced endothelial PGI2 synthesis. Although all three PUFA (3-33 μM) were found to stimulate release from neutrophil-specific granules, only 22:6 and 20:4 could stimulate release of the azurophilic granules containing elastase to any significant extent. Saturated fatty acids (20:0 and 22:0) and the methyl ester of 22:6 did not cause either neutrophil-mediated endothelial detachment or degranulation. We conclude that neutrophils pretreated with 22:6 or 20:4 but not 20:5 can decrease endothelial integrity through detachment involving neutrophil elastase. These findings may have important implications for the dietary use of fish oils rich in n-3 fatty acids.

Original languageEnglish
Pages (from-to)590-598
Number of pages9
JournalJournal of Leukocyte Biology
Issue number6
Publication statusPublished or Issued - 1993
Externally publishedYes


  • cytotoxicity
  • detachment
  • fish oils
  • granulocytes
  • polyunsaturated fatty acids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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