Second messenger function of arachidonic acid lipoxygenation products in human natural killer cell lysis?

M. Jondal, C. Kullman, P. Rossi, J. A. Lindgren

Research output: Contribution to journalArticle

Abstract

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-1-m-(trifluoromethyl)-phenyl-2-pyrazoline (BW 755C), and indomethacin. All drugs inhibited NK lysis at the post-target cell-binding level at concentrations that also suppressed lipoxygenation or 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-dependent systems. Further evidence of the involvement of arachidonic acid lipoxygenation was found as NK activity could be reconstituted to NDGA-suppressed effector cells with several metabolites such as LTB 4, LTB 4 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 be further investigated.

Original languageEnglish
Pages (from-to)285-294
Number of pages10
JournalScandinavian Journal of Immunology
Volume22
Issue number3
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Immunology

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