Neutrophil producing capacity of 5-lipoxygenase metabolites of arachidonic acid after major surgery.

Abstract

It is well known that patients who undergo surgical operations have a high risk of infection and sepsis. One explanation for this high risk may be a depression of neutrophil functions at the postoperative period. In the present study, the effects of surgical stresses on neutrophil functions were studied in ten patients who underwent general anesthesia and major surgery. The neutrophil functions especially focused on were the producing capacities of 5-lipoxygenase metabolites of arachidonic acid such as Leukotriene B4 (LTB4), LTC4, LTD4, 6-trans-LTB4, and w-oxidation products of LTB4. Neutrophils were stimulated with calcium-ionophore A23187 (2x10(-5) M) in the presence of arachidonic acid (5x10(-5) M) for 5 minutes at 37 degrees C. The arachidonic acid metabolites were extracted by methanol. After centrifugation, the supernatant of the mixture was concentrated and applied to a C-18 column on reversed phase high performance liquid chromatography (RP-HPLC) system, monitoring the absorbance at 280 nm. In all cases, the LTB4 production significantly increased postoperatively with an increment of 6-trans-LTB4 and w-oxidation products of LTB4. The LTC4 production, by contrast, significantly decreased postoperatively. LTD4 production was observed at neither pre nor postoperative periods. The total amount of LTA4 metabolites at the postoperative period, including LTB4, LTC4, and 6-trans-LTB4, increased 1.2 times compared with that at preoperative period. This indicates the possibility of the alteration of the neutrophil metabolism in 5-lipoxygenase cascade, the increment of LTA4 generation and the change of LTA4 metabolism from LTC4 synthesis to LTB4 generating pathway.