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Tumor necrosis factor release by human monocytes stimulated with platelet-activating factor

  • PAF and Signal Transduction
  • Published:
Lipids

Abstract

Platelet-activating factor (PAF) is a low molecular weight phospholipid which enhances human monocyte cytotoxicity for tumor cells. In the current studies, the capacity of PAF to stimulate release of tumor necrosis factor α (TNFα) by human monocytes was assessed. PAF induced maximal TNFα synthesis 2–3 hr after monocyte stimulation as assessed by dot blotting of cell-associated TNFα using polyclonal anti-TNF antibody. Maximal net release of TNFα occurred 5–16 hr after monocyte stimulation, as assessed by a specific ELISA. Dose-response studies revealed that a maximal two- to three-fold increase in release of TNFα occurs at 10–100 pM PAF. LysoPAF and the optical isomer of PAF did not stimulate release of TNFα, suggesting that stimulation is mediated by specific PAF receptors. Scatchard analysis of [3H]PAF binding to monocyte membranes revealed 651±495 binding sites/monocyte with a Kd of 4.7±4.2×10−10M. PAF is a structurally unique activator of monocytes whose interactions with TNFα and other cytokines may be critical to host defense against tumors.

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Abbreviations

BSA:

bovine serum albumin

enantioPAF:

3-O-hexadecyl-2-acetyl-sn-glycero-1-phosphocholine

IFNγ:

γ Interferon

lysoPAF:

1-O-hexadecyl-sn-glycero-3-phosphocholine

PGE2 :

prostaglandin E2

MTT:

[3-(4,5-dimethylthiazol)2-yl)-2,5-diphenyltetrazolium bromide]

PAF:

platelet-activating factor, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine

TNFα:

tumor necrosis factor α

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Authors and Affiliations

  1. Dept. of Medicine, Veterans Administration Medical Center, 4150 Clement Street, 94121, San Franciso, CA

    N. M. Ruis, J. K. Rose & F. H. Valone

Authors
  1. N. M. Ruis
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  2. J. K. Rose
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  3. F. H. Valone
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Ruis, N.M., Rose, J.K. & Valone, F.H. Tumor necrosis factor release by human monocytes stimulated with platelet-activating factor. Lipids 26, 1060–1064 (1991). https://doi.org/10.1007/BF02536502

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  • DOI: https://doi.org/10.1007/BF02536502

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