ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Human natural killer (NK) cells were tested in the presence of several fatty acid oxygenase inhibitors such as nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid, 3-amino-l-m-(trinuoromethyl)-phenyl-2-pyrazoline (BW 755C). and indomcthacin. All drugs inhibited NK lysis at the post-target cell-binding level at concentrations that also suppressed lipoxygenation of arachidonic acid, suggesting that such reactivity may be required for effector cell triggering. NDGA gave a 50% NK cell inhibition in the range of 10-30 μM and also suppressed antibody-dependent and lectin-dependenl systems. Further evidence of the involvement of arachidonic acid lipoxygenation was found as NK activity could be reconstituled to NDGA-suppressed effector cells with several metabolites such as LTB4. LTB4 analogues, and hydroxyeicosatetraenoic acids lipoxygenated at C-5, C-12, and C-15. Cyclic nucleotides such as cGMP and cAMP could also reconstitute activity with optimal effects at approximately 10−8 M. The combined evidence is compatible with a model for triggering lysis in which lipoxygenation products have a second messenger function. Whether arachidonic acid lipoxygenation is necessary for effector cells at all different activation/differentiation stages and whether the lipoxygenation products activate guanylic cyclase, protein kinase C, or some other target molecule remain to he further investigated.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-3083.1985.tb01883.x
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