INFLUENCE OF HEXADECYLPHOSPHOCHOLINE ON THE RELEASE OF TUMOR-NECROSIS-FACTOR AND NITROXIDE FROM PERITONEAL-MACROPHAGES IN-VITRO

Hexadecylphosphocholine (HPC) has been investigated intensively for it s cancerostatic properties. One explanation for the mechanism of actio n of HPC assumes that it plays a role in stimulation of the immune sys tem. In particular, its potency to activate macrophages has already be en 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 necro sis 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 d ifferent primer/trigger combinations with lipopolysaccharide (LPS). A weak change in morphology was revealed by electron microscopy, if macr ophages were harvested from mice previously treated with HPC or HPC mu ltilamellar vesicles. This observation was quantified by the measureme nt of NO, TNF and cytotoxic activity of the peritoneal macrophages. A specific release of NO was induced by the combination of in vivo treat ment with liposomal HPC and subsequent stimulation by LPS in vitro. Th is process started only after 12 h of in vitro incubation of macrophag es 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 pr imed with liposomal HPC and then triggered with LPS.