leukotriene-b4 and musk

To investigate the effects of musk-1, a glucoprotein component isolated from the water extract of musk, on arachidonic acid metabolizing enzymes, which include phospholipase A2(PLA2), 5-lipoxygenase (5-LO), and cyclooxygenase (COX), in rat polymorphonuclear leukocytes, an in vitro incubation system with rat polymorphonuclear leukocytes or homogenate supernatant of the same cells was used. In comparison with control, musk-1 at final concentrations of 1-100 micrograms/ml can increase AA release from PMNL by 6.0%-21.6%, decrease LTB4 biosynthesis in homogenate supernatant of the cells by 9%-81%, but increase 6-keto-PGF1 alpha production by 18.2%-85.4%.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonate 5-Lipoxygenase; Fatty Acids, Monounsaturated; Female; Leukotriene B4; Male; Neutrophils; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar

The present work was designed to further study the mechanism of the anti-inflammatory action of musk from the viewpoint of arachidonic acid (AA) metabolism: 1) effect on AA release; 2) action on leukotriene B4 (LTB4) and 5-HETE biosyntheses. Leukocytes obtained from rat inflammatory exudate by i.p. injection of 1% carrageenan were labelled with 14C-AA at 37 degrees C for 2 h. The 14C-AA labelled cells were incubated with the water soluble fraction of musk (MWF) and stimulated with calcium ionophore A23187 to release AA. The radioactivity released from the labelled leukocytes was determined as a criterion of AA release. In order to observe the influence of musk on the biosyntheses of LTB4 and 5-HETE, leukocytes were incubated with MWF and AA, and then stimulated with A23187. The LTB4 and 5-HETE produced were determined by RP-HPLC. The results showed that AA release decreased to 50-70% of the control at MWF concentration of 6.25-37.5 micrograms/ml. The biosyntheses of LTB4 and 5-HETE were not affected. However, AA release increased to 1.5-fold at the MWF concentration of 400 micrograms/ml. At the same time, biosyntheses of LTB4 and 5-HETE decreased by 66.7 and 90%, respectively, as compared with controls. This result indicates that MWF not only inhibited phospholipase A2 (PLA2) activity, but also prevented AA peroxidation and inhibited LTB4 biosynthesis. These results suggest that inhibition of the AA metabolic pathway may play a major role in the mechanism of the anti-inflammatory action of musk.

Topics: Animals; Arachidonic Acid; Carrageenan; Exudates and Transudates; Fatty Acids, Monounsaturated; Hydroxyeicosatetraenoic Acids; Inflammation; Leukocytes; Leukotriene B4; Rats