Application of zymosan in medicine is limited because of its side effects, since the native granules of zymosan directly activate serum complement components and phagocytic cells. In this regard, it was decided at the outset (ex vivo) to incorporate the granules of zymosan in the neutrophils, and only then inject these “loaded” zymosan neutrophils into the bloodstream. Our experiments showed a total inhibition of the weight accretion of both tumor affected liver (from 5220±963 to 1327±219mg) and spleen (from 328±29 to 187±64mg) of mice. Thus these data showed that even on the 17th day after a single intravenous injection zymosan-treated neutrophils persist expressed manifestations of anti-tumor activity in the liver and spleen, that may be basis for using this method for antimetastatic preventive measures in liver and other localizations
melanoma, neutrophils, zymosan, glucan, liver tumors, spleen
1. BesednovaNN, IvanushkoLA, ZvyagintsevaTN, Elyak-ovaLA (2000). Immunotropic properties of 1→3; 1→6 -β-D-glucans [Immunotropnye svoystva 1→3; 1→6-β-D-g-lyukanov]. Antibiotiki i khimioterapiya, 45(2), 37-44.
2. LyubimovGY, LyubimovAG (2011). Effect of zymosan incorporated in autologous macrophages on metastatic growth of B16melanoma in the mice’s liver [Vliyanie in-korporirovannogo v autologichnye makrofagi zimozana na metastaticheskiy rost melanomy B16 v pecheni myshey]. Rossiyskiy immunologicheskiy zhurnal, 5(14), 309-314
3. LyubimovGY, LyubimovAG, MenshchikovaEB,KozlovVA (2016). Preventive intravenous injection of zymosan-treated neutrophils inhibits the growth of B16 melanoma in the liver and spleen of mice [Preventivnoe vnutrivennoe vvedenie zimozan-obrabotannykh neytro-filov podavlyaet rost melanomy B16 v pecheni i selezenke myshey]. Sibirskiy nauchnyy meditsinskiy zhurnal, 36(2), 45-49.
4. MayanskiyDN, TsyrendorzhievDD (1989). Reactivity of lung and liver macrophages of normal and previously stimulated animals [Reaktivnost’ makrofagov legkikh i pecheni normal’nykh i predvaritel’no stimulirovannykh zhivotnykh]. Patologicheskaya fiziologiya i eksperimen-tal’naya terapiya,(4), 44-48.
5. MayanskiyDN, TsyrendorzhievDD, YonkerAM(1990). Induction of granulomatous liver inflammation by non-infectious particles [Induktsiya granulematoznogo vospaleniya pecheni neinfektsionnymi chastitsami]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, (5), 45-49
6. AkramieneD, KondrotasA, DidziapetrieneJ, Keve-laitisE (2007). Effects of β-glucans on immune system. Medicina (Kaunas), 43(8), 597-606.
7. DeimannW, FaimiHD (1980). Induction of focal Hemopoiesis in adult rat liver by glucan, a macrophage activator. Laboratory Investigation, 42(2), 217-225.
8. FaradjiA, BohbotA, Schmitt-GoguelM, RoeslinN, DumontS, WieselML, LallotC, EberM, BartholevnsJ, Poin-dronP, MorandG, WitzJP, OberlingF (1991). Phase I trial of intravenous infusion of ex-vivo-activated autologous blood-derived macrophages in patients with non-small-cell lung cancer: toxicity and immunomodulatory effects. Cancer Immunol. Immunother., 33(5), 319-326.
9. GregoryAD, HoughtonAM (2011). Tumor-associ-ated neutrophils: new targets for cancer therapy. Cancer Res., 71(7), 2411-2416
10. HoughtonAM (2010). The paradox of tumor-as-sociated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle, 9(9), 1732-1737.
11. LalaA, LindemannRA, MiyasakiKT (1992). The differential effects of polymorphonuclear leukocyte secre-tion on human natural killer cell activity. Oral Microbiol. Immunol., 7(2), 89-95.
12. MorikawaK, TakedaR, YamazakiM, MizunoD(1985). Induction of tumoricidal activity of polymor-phonuclear leukocytes by a linear beta-1,3-D-glucan and other immunomodulators in murine cells. Cancer Res., 45(4), 1496-1501
13. PekarekLA, StarrBA, ToledanoAY, SchreiberH (1995). Inhibition of tumor growth by elimination of granulocytes. J. Exp. Med., (181), 435-440.
14. QiC, CaiY, GunnL, DingC, LiB, KloeckerG, QianK, VasilakosJ, SaijoS, IwakuraY, YanelliJR, YanJenJ (2011). Differential pathways regulating innate and adaptive anti-tumor immune responses by particulate and soluble yeast-derived B-glucans. Blood, 117(25), 6825-6836.
15. SchirmerWJ, SchirmerJM, NaffGB, FryDE(1988). Contribution of toxic oxygen intermediates to complement-induced reductions in effective hepatic blood flow. J. Trauma, 28(9), 1295-1300.
16. SchirmerWJ, SchirmerJM, NaffGB, FryDE(1988). Systemic complement activation produces he-modynamic changes characteristic of sepsis. Arch. Surg., 123(3), 316-321.
17. SmithHA, KangY (2013). The metastasis-pro-moting roles of tumor-associated immune cells. J. Mol. Med. (Berl.), 91(4), 411-429
18. SuzukiT, OhnoN, ChibaN, MiuraNN, AdachiY, YadomaeT (1996). Immunopharmacological activity of the purified insoluble glucan, zymocel, in mice. J.Pharm. Pharmacol., 48(12), 1243-1248.
19. TateishiT, OhnoN, AdachiY, YadomaeT(1997). Increases in Hematopoietic responses caused by β-glucans in mice. Biosci. Biotech. Biochem, 61(9),1548-1553.
20. UnderhillDM (2003). Macrophage recognition of zymosan particles. J.Endotoxin Res.. (3), 176-180.
21. VolmanTJ, HendriksT, GorisRJ (2005). Zy-mosan-induced generalized inflammation: experimental studies into mechanisms leading to multiple organ dys-function syndrome. Shock, 23(4), 291-297.
22. WilliamsDL, SherwoodER, McNameeRB,JonesEL, DiLuzioNR (1985).Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease. Hepatology, 5(2), 198-206.
23. WinnAA, MiyakawaK, MiyataE, DranoffG,TakeyaM, TakahashiKL (2001). Role of granulocyte/macrophage colony-stimulating factor in zymocel-induced hepatic granuloma formation. Am. J. Pathol., 158(1), 131-145.
24. WoolesWR, DiLuzioNR (1964). The phagocytic and proliferative response of the reticuloendothelial sys-tem following glucan administration. J. Reticuloendothel. Soc., (1), 160-169
