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Alkylphosphocholine-induced production of nitric oxide and tumor necrosis factor α by U 937 cells

  • Ines Eue
  • Reiner Zeisig
  • Dieter Arndt
Original Paper Experimental Oncology

Abstract

The human histiocytic cell line U937, which expresses a number of monocyte markers and properties, was investigated with regard to its ability to be activated for NO and tumor necrosis factor (TNF) release after treatment with alkylphosphocholines (APC) and APC liposomes. Using APC multilamellar vesicles (MLV) a clear dose-dependent increase of NO production could be demonstrated for U 937 cells, whereas the corresponding soluble substances had no effect. The time course of NO release was characterised by a peak between 2 h and 12 h and a strong decrease after 24 h. LPS caused no NO release nor the production of TNF in U 937 cells. The simultaneous incubation of the cells with lipopolysaccharide and APC or APC-MLV, led to a strong increase in TNF production. Closer investigation of the time sequence of this synergistic effect demonstrated that cells, that had first been treated with hexadecylphosphocholine (HPC)-MLV and 4 h later with lipopolysaccharride secreted significantly more TNF into the supernatants than in the experiment where both substances were added simultaneously. From these results it was concluded that APC-MLV are possibly able to act as a primer in the process of lipopolysaccharide mediated TNF induction. Furthermore, a positive influence of phorbol 12-myristate 13-acetate (PMA) on the ability of U 937 cells to produce TNF following a treatment with HPC or HPC-MLV could be observed. PMA-pretreated cells were shown to release much more TNF compared to control cells, which led to the supposition that the immunomodifying activity of APC becomes effective only in more highly differentiated cell types.

Key words

Miltefosin Hexadecylphosphocholine Alkylphosphocholine Liposomes MLV Nitric oxide Tumour necrosis factor Macrophage Macrophage activation 

Abbreviations

APC

alkylphosphocholines

DPC

dodecylphosphocholine

HPC

hexadecylphosphocholine

TPC

tetradecylphosphocholine

MLV

multilamellar vesicles

PMA

phorbol 12-myristate 13-acetate

TNF

tumour necrosis factor

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Ines Eue
    • 1
  • Reiner Zeisig
    • 1
  • Dieter Arndt
    • 1
  1. 1.Max Delbrück Centre for Molecular MedicineBerlinGermany

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