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United States Department of Agriculture

Agricultural Research Service

Title: Fumonisin B1 Inhibits Lymphocyte Proliferation Through a Nitric Oxide Dependent Mechanism

Authors
item Dombrink Kurtzman, Mary Ann
item Gomez-Flores, Ricardo - UNIV COLLEGE MED, PEORIA
item Weber, Richard - UNIV COLLEGE MED, PEORIA

Submitted to: Immunopharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 16, 2000
Publication Date: N/A

Interpretive Summary: Our study was conducted to investigate the effect of the mycotoxin, fumonisin B1, on the functioning of lymphocytes and macrophages. Lymphocytes are white blood cells, and macrophages are cells of the immune system that play an important role in the initiation and regulation of the immune response. The cells were isolated from rats and exposed to fumonisin B1 in culture. Results indicated that fumonisin B1 was able to activate macrophages, resulting in stimulation of the enzyme, inducible nitric oxide synthase, production of nitric oxide, and suppression of lymphocyte proliferation. When a specific inhibitor of the enzyme was present, fumonisin B1 caused the lymphocytes to proliferate, suggesting that the mycotoxin can act as a tumor promoter if nitric oxide is not present. It was concluded that stimulation of the enzyme can be considered a previously unrecognized effect of fumonisin B1 exposure and that nitric oxide may be responsible for some of the effects observed in animals. Studies which provide a better understanding of fumonisin-related effects should result in increased safety of both food and animal feed.

Technical Abstract: We investigated the effect of fumonisin B1 on rat splenic macrophage and lymphocyte functions. Pretreatment (24 h) with fumonisin B1 (1, 10, and 100 ug/ml) significantly (p < 0.01) stimulated nitric oxide production by resident macrophages (0.12 +/- 0.014, 0.65 +/- 0.006, and 1.10 +/- 0.019 nmol nitrate/5 X 104 cells, respectively), compared with the response of untreated macrophages (0 nmol nitrate/5 X 104 cells), and potentiated that of IFN-y (50 U/ml)-activated macrophages (0.88 +/- 0.051, 1.24 +/- 0.020, and 1.11 +/- 0.072 nmol nitrate/5 X 104 cells, respectively), compared with the response of IFN-y-treated macrophages (0.42 +/- 0.028 nmol nitrate/5 X 104 cells), after 72 h of culture. Fumonisin B1 (1 and 10 ug/ml) and IFN-y acted synergistically to activate nitric oxide production. Fumonisin B1 did not induce proliferation of mitogen-untreated splenic lymphocytes, and lymphocytes treated with Con A (1.25 and 2.5 ug/ml), anti-T-cell receptor(alphabeta) (antiTCR), IL-2 or antiTCR + IL-2. However, fumonisin B1 (100 ug/ml) significantly (p < 0.05) increased splenic lymphocyte proliferation to Con A at 5 ug/ml. When nitric oxide was inhibited using n(G)-monomethyl-L-arginine (NMA), fumonisin B1 (10 and 100 ug/ml) significantly (p < 0.05) enhanced proliferative responses of mitogen-untreated (1.3-fold increase), Con A (1.25 to 5 ug/ml)-treated (1.46- to 2.62-fold increases), and antiTCR, IL-2 or antiTCR + IL-2-treated (1.72- to 2.60-fold increases) splenic cells. Results suggest that fumonisin B1 is a potent activator of macrophage and lymphocyte functions in vitro, and a potential growth- stimulating agent for both immune and nonimmune cells.

Last Modified: 10/20/2014
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