Neutrophils pretreated with docosahexaenoic acid or arachidonic acid, but not eicosapentaenoic acid, increased endothelial detachment through a mechanism involving neutrophil elastase.
Does pretreatment of neutrophils with docosahexaenoic acid or arachidonic acid increase neutrophil-mediated injury of cultured endothelial cells compared to eicosapentaenoic acid?
Docosahexaenoic acid and arachidonic acid, but not eicosapentaenoic acid, can induce neutrophil-mediated injury of cultured endothelial cells via neutrophil elastase, which may have implications for dietary fish oil use.
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 docosahexaenoic (22:6, n-3) and arachidonic (20:4, n-6) acids at 10-40 microM 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 microM) 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.
Bates et al. (Wed,) reported a other. Docosahexaenoic acid (22:6, n-3) and arachidonic acid (20:4, n-6) vs. Eicosapentaenoic acid (20:5, n-3) and saturated fatty acids was evaluated on Endothelial detachment and neutrophil degranulation. Neutrophils pretreated with docosahexaenoic acid or arachidonic acid, but not eicosapentaenoic acid, increased endothelial detachment through a mechanism involving neutrophil elastase.
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