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Effect of platelet-activating factor on tumor necrosis factor-induced superoxide generation from human neutrophils. Possible involvement of G proteins

  • PAF and Signal Transduction
  • Published:
Lipids

Abstract

The effect of platelet-activating factor (PAF) and of two specific PAF antagonists on tumor necrosis factor (TNF) induced superoxide production by human polymorphonuclear neutrophils (PMN) was examined. PAF alone (0.1 pM to 0.1 nM) failed to evoke superoxide production; however, when PAF was added for 10 min to cells upon prior incubation with 10 ng/mL TNF for 50 min, superoxide production was significantly enhanced as compared to that induced by TNF alone. Maximum amplification (+30%) was obtained with 10 pM PAF; however, the effect was completely abolished by two structurally unrelated PAF antagonists, BN 52021 and BN 52111. The antagonists also decreased by 25% the superoxide production elicited solely by TNF, implicating the involvement of endogenous PAF in this process. Pretreatment of the PMN with either pertussis or cholera toxin attenuated the PAF amplified superoxide production in TNF stimulated cells, suggesting that G proteins sensitive to these toxins may be involved in the mechanisms controlling amplification.

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Abbreviations

ADP:

adenosine-5′-monophosphate

BN 52021:

ginkgolide B

BN 52111:

2-heptadecyl-2-methyl-4-[5-(pyridinium-pentylcarbonyloxymethyl)]-1,3-dioxolane bromide

BSA:

bovine serum albumin

FMLP:

formyl-methionyl-leucyl-phenylalanine

GTP:

guanosine-5′-triphosphate

NADPH:

nicotinamide adenine dinucleotide, reduced form

PAF:

platelet-activating factor

PBS:

phosphatebuffered saline

PMN:

polymorphonuclear neutrophils

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Clinical Research Unit Burn Center, 92141, Clamart, France

    Philipe Koltz, Jean Guilbaud & Monique Paubert-Braquet

  2. Institut Henri Beaufour, 17, avenue Descartes, F-92350, Le Plessis Robinson, France

    Pierre Braquet & David Hosford

Authors
  1. Pierre Braquet
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  2. David Hosford
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  3. Philipe Koltz
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  4. Jean Guilbaud
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  5. Monique Paubert-Braquet
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Braquet, P., Hosford, D., Koltz, P. et al. Effect of platelet-activating factor on tumor necrosis factor-induced superoxide generation from human neutrophils. Possible involvement of G proteins. Lipids 26, 1071–1075 (1991). https://doi.org/10.1007/BF02536504

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  • DOI: https://doi.org/10.1007/BF02536504

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