Influence of hexadecylphosphocholine on the release of tumor necrosis factor and nitroxide from peritoneal macrophages in vitro.
Hexadecylphosphocholine (HPC) has been investigated intensively for its cancerostatic properties. One explanation for the mechanism of action of HPC assumes that it plays a role in stimulation of the immune system. In particular, its potency to activate macrophages has already been recognised for different lyso- and ether lipids. Important steps in the cascade for developing cytotoxic effects of macrophages on tumor cells are the release of nitric oxide radicals (NO) and/or tumor necrosis factor (TNF). The aim of our study was to examine the role of HPC as primer and/or trigger for macrophage activation to cytotoxicity. In our experiments we used HPC in free (micellar) or liposomal form in different primer/trigger combinations with lipopolysaccharide (LPS). A weak change in morphology was revealed by electron microscopy, if macrophages were harvested from mice previously treated with HPC or HPC multilamellar vesicles. This observation was quantified by the measurement of NO, TNF and cytotoxic activity of the peritoneal macrophages. A specific release of NO was induced by the combination of in vivo treatment with liposomal HPC and subsequent stimulation by LPS in vitro. This process started only after 12 h of in vitro incubation of macrophages with the endotoxin. The release of TNF was dependent of the primer/trigger combination used. A moderate priming effect was obtained with HPC in liposomal form independently of the trigger. On the other hand, liposomes as priming agents were found to induce a dramatic increase in TNF release after in vitro coculture with the trigger LPS. The high release of NO and TNF is accompanied by only a weak increase in tumor cytostasis. The best results were once more found with macrophages primed with liposomal HPC and then triggered with LPS.
Zeisig
R
R
Max Delbrück Center for Molecular Medicine, AG Phospholipide, Berlin-Buch, Germany.
Rudolf
M
M
Eue
I
I
Arndt
D
D
D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes / Q000008:administration & dosage; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D010767:Phosphorylcholine; D009569:Nitric Oxide; C039128:miltefosine