Production of reactive oxygen species by neutrophils was analyzed by a chemiluminometric method in the presence of luminol in ten healthy donors, eight patients with gastric cancer and ten patients with gastric precancer. The neutrophil chemiluminominescence response to recombinant tumour necrosis factor (rTNF) was almost five times lower in the gastric patients when compared with healthy donors and precancer patients. The chemiluminescence response to zymosan was decreased only in the gastric cancer patients with chemiluminescence index activation (CTNF) less than 1. The observed changes of neutrophil functions are thought to result in a decrease of neutrophil cytotoxic activity in gastric cancer patients.
It is shown that ganglioside GM1 in picomolar concentrations stimulates the phorbol-12-myristate-13-acetate (PMA)-induced generation of active forms of oxygen by neutrophils and peritoneal macrophages. GM1 (10 -H M) is found to enhance the luminoldependent chemiluminescence induced by 10 -s M PMA in mouse macrophages in comparison with the effect of PMA alone.
Key Words: gangliosides; phagocytes; oxidative burstUntil recently, the involvement of the signal transduction systems in the regulation of free radical reactions has been shown solely for phagocytes [1]. Previously we found that gangliosides and phorbol-12-myristate-13-acetate (PMA) are capable of inhibiting lipid peroxidation (LPO) in brain synaptosomes, whereas a penetrating cAMP analog reduces and polymyxin B almost completely abolishes the inhibiting effect of these compounds [2]. These data suggest that, since these compounds act as transmitters in the signal transduction systems, the effect of gangliosides on free'radical processes is mediated through these systems. Gangliosides are membrane constituents not only in nervous but also in other tissues. They may be released from immune ceils and affect the functional activity of lymphocytes [3][4][5]. However, there are no data on The objective of the present investigation was to study the effect of nano-and picomolar ganglioside concentrations on the generation of active forms of oxygen by mouse macrophages and human neutrophils in response to low concentrations of phorbol esters. Such data are of great interest for understanding the mechanism of the immunemodulatory effect of gangliosides and, probably, the mechanism of their neurotrophic effects [2].
MATERIALS AND METHODSThe experiments were carried out on primed peritoneal macrophages of BALB/c mice. The mice were injected intraperitoneaUy with 1 ml sterile 10% peptone in physiological saline. Forty-eight hours later the animals were killed, and the peritoneal cavity was washed with medium 199 containing 15% bovine serum, 5 U/ml heparin, 1000 U/ml penicillin, and 100 Ixg/ml streptomycin. The obtained exudate was placed in special measuring cuvettes (2• cells per cuvette). After a 2-hour
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