Ricin-induced toxicity in the macrophage J744A.1 cells: the role of TNF-alpha and the modulation effects of TNF-alpha polyclonal antibody.
Ricin is a natural toxin of the castor beans (Ricinus communus). We studied the time- and concentration-dependent effects of ricin on the release of TNF-alpha and lactate dehydrogenase (LDH), as well as the modulation of the ricin-induced effects by TNF-alpha antibody in the J774A.1 cells. When added at concentrations ranging from 0 to 1000 ng/mL, ricin caused concentration-dependent increases in the release of TNF-alpha after incubation for 12 to 24 hours. Concentration-dependent increases in the leakage of LDH were also observed after incubation of the cells with those concentrations of ricin for 24 to 48 hours. Addition of 5 units/mL of rabbit anti-mouse TNF-alpha polyclonal antibody (TNF-alpha antibody) 2 hours prior to the addition of ricin resulted in a decrease in the ricin-induced toxicity, indicated by the release of LDH by the cells. However, when added at concentrations higher than 5 units/mL, the antibody resulted in either no effect or an increase in the ricin-induced LDH leakage. These results suggest that secretion of TNF-alpha by the macrophages in response to ricin plays a significant role in the toxicity of ricin and that TNF-alpha antibody can antagonize the effects of ricin in this cell line when added at relatively low concentrations.
Hassoun
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E
The University of Toledo, College of Pharmacy, OH 43606, USA. ehassou@utnet.utoledo.edu
Wang
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X
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D011817:Rabbits; D012276:Ricin / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D012276:Ricin; D007770:L-Lactate Dehydrogenase