| Abstrakt: |
CI-986 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione, choline salt) was evaluated for its effect on arachidonic acid metabolism by human neutrophils in response to different stimuli. Leukotriene B (LTB) release in response to calcium ionophore A23187 was 15 to 35 fold greater than the responses to N-formyl-methionyl-leucyl-phenylalanine (FMLP) or serum-opsonized zymosan (SOZ), respectively, while the thromboxane B (TXB) release response was similar for the three stimuli tested. CI-986 inhibited the release of LTB and TXB in response to A23187 with ICs of 63.4 and 1.6 µM, respectively. In comparison, the compound inhibited SOZ-stimulated LTB release with an IC of 11.2µM, while having no effect on TXB at concentrations up to 100 µM. Conversely, CI-986 inhibited FMLP-stimulated LTB release by 42% at 100 µM, while inhibiting TXB release with an IC of 0.13 µM. These results demonstrate a stimulus-dependent inhibitory effect of CI-986 on human neutrophil eicosanoid metabolism. [ABSTRACT FROM AUTHOR] |
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