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/

Previously published work has indicated that polyunsaturated fatty aci ds (PUFA) may enhance neutrophil-mediated damage to host tissues. We h ave found that endothelial detachment was significantly increased by n eutrophils pretreated with docosahexaenoic (22:6, n-3) and arachidonic (20:4, n-6) acids at 10-40 muM but not by eicosapentaenoic acid (20:5 , n-3). Endothelial cell lysis as measured by Cr-51 release was unaffe cted. The extent of detachment was dependent on both fatty acid and ne utrophil pretreatment concentrations. A specific leukocyte elastase in hibitor abrogated the increased detachment but catalase had no effect. Measurement of prostaglandin 12 synthesis as an alternative nonlytic assay of endothelial function indicated that 20:4 but not 20:5 was abl e to stimulate neutrophil-induced endothelial PGI2 synthesis. Although all three PUFA (3-33 muM) were found to stimulate release from neutro phil-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 d id not cause either neutrophil-mediated endothelial detachment or degr anulation. We conclude that neutrophils pretreated with 22:6 or 20:4 b ut not 20:5 can decrease endothelial integrity through detachment invo lving neutrophil elastase. These findings may have important implicati ons for the dietary use of fish oils rich in n-3 fatty acids.