Lipoxins A4 and B4 inhibit leukotriene B4 generation from human neutrophil leukocyte suspensions

Lipoxins A4 and B4 (5,6,15L-trihydroxy-7,9,11,13-eicosatetraenoic and 5D,14,15-trihydroxy-6,8,10,12-eicosatetraenoic acids, respectively) were examined in several biological systems and have proven to have many different activities from those of other eicosanoids. Cultured human polymorphonuclear leukocytes were preincubated with LXA and B and their ability to inhibit leukotriene B4 generation was assessed after incubation with the calcium ionophore A23187. The preincubation time of neutrophils with lipoxin A4 and B4 was 15 min. After that time the cells were incubated for 6 min with A23187 (5 microM) for the release of LTB4. We found that the pretreatment of neutrophils with lipoxins inhibited the release of LTB4 by A23187-stimulated PMNs. Nordihydroguaiaretic acid (NDGA) (10 microM), used as a control, strongly inhibited the generation of LTB4. Since LTB4 has been shown to be a modulator of cellular immunity, our data suggest that lipoxin A4 and B4 can contribute to the immunosuppression via inhibition of LTB4 generation. Moreover, the inhibition of LTB4 by lipoxins in neutrophils could have an important regulatory role in inflammation.