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Tumour necrosis factor (TNF) as a mediator of macrophage helminthotoxic activity
Author(s) -
JAMES STEPHANIE L.,
GLAVEN JUDITH,
GOLDENBERG STANLEY,
MELTZER MONTE S.,
PEARCE EDWARD
Publication year - 1990
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/j.1365-3024.1990.tb00932.x
Subject(s) - monokine , tumor necrosis factor alpha , schistosoma mansoni , lymphokine , biology , macrophage , cytotoxic t cell , immunology , cytotoxicity , macrophage activating factor , in vitro , effector , necrosis , cytokine , microbiology and biotechnology , immune system , interleukin , schistosomiasis , helminths , biochemistry , genetics
Summary Lymphokine‐activated macrophages are cytotoxic for larvae of the helminth parasite Schistosoma mansoni. That soluble secreted factors may mediate this cytotoxicity was suggested by the observation that culture supernatant fluids from stimulated macrophages also exhibited larvacidal activity. These fluids contain the monokine tumour necrosis factor (TNF). Several observations indicated that TNF is directly toxic to schistosome larvae. Cytotoxic sera taken from BCG‐ or S. mansoni ‐immunized mice after endotoxin challenge killed schistosomula in vitro , and upon gel filtration the larvacidal factor(s) in the sera co‐eluted with the tumoricidal activity defined as TNF. Recombinant‐derived TNF exhibited direct toxicity to schistosomula at high concentrations, or at lower concentrations in the presence of IFNγ. The larvacidal activity of macrophage supernatant fluids was abrogated by addition of either anti‐TNF antisera or Zn +2 , which has been shown to inhibit TNF‐induced damage of tumour cells. Anti‐TNF and Zn +2 likewise suppressed schistosomulum killing by lymphokine‐activated peritoneal macrophages or the IC‐21 macrophage line, indicating that TNF also plays a role in the effector mechanism of larval killing by whole cells.