Hydrogen peroxide as a tumoricidal mediator of murine polymorphonuclear leukocytes induced by a linear beta-1,3-D-glucan and some other immunomodulators.
Polymorphonuclear leukocytes (PMN) of mice can destroy tumor cells effectively in vitro in the presence of antitumor polysaccharide, linear beta-1, 3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK), and some other immunomodulators. In the present study, we investigated the mechanism of the tumoricidal activity of PMN induced by these immunomodulators and especially TAK. The TAK-induced PMN cytotoxicity was concluded to involve hydrogen peroxide from the following results: (a) the cytotoxicity depended on glucose consumption; (b) it was almost completely inhibited by catalase but not affected by superoxide dismutase; (c) it was not reduced by cyanide or azide, which are inhibitors of myeloperoxidase; (d) it was not affected by scavengers of singlet oxygen or hydroxyl radical; (e) release of hydrogen peroxide from PMN was observed by the addition of TAK; (f) MM46 target cells were lysed directly by hydrogen peroxide in the absence of myeloperoxidase; (g) the supernatant of PMN in the presence of TAK, tested as a stable cytotoxic factor, did not have cytotoxic activity, and protease inhibitors had no effect on this cytotoxicity. These results suggest that hydrogen peroxide is a direct cytotoxic mediator in TAK-induced PMN cytotoxicity. Next, the mechanism of PMN cytotoxicities induced by other immunomodulators was also examined and was compared with that induced by TAK. The results suggest that hydrogen peroxide is also important for these cytotoxicities whereas, unlike the results with TAK, the H2O2:halide:myeloperoxidase system may partly participate in the cytotoxicities with some immunomodulators.
Morikawa
K
K
Kamegaya
S
S
Yamazaki
M
M
Mizuno
D
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005609:Free Radicals; D005936:Glucans / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009195:Peroxidase / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D047071:beta-Glucans
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D003486:Cyanides; D005609:Free Radicals; D005936:Glucans; D011480:Protease Inhibitors; D047071:beta-Glucans; C033363:beta-1,3-glucan; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase