The importance of leukotrienes in mast cell-mediated Toxoplasma gondii cytotoxicity.
Mast cells participate in the host defense against parasites. Mast cells release leukotrienes (LTs), potent 5-lipoxygenase (LO) products of arachidonic acid well-known to be involved in the inflammatory process. After incubation with Toxoplasma gondii, mast cells were found to degranulate and release LTB4; this interaction damages the tachyzoites. This mast cell activity against the tachyzoites was inhibited by the 5-LO inhibitor A-63162 and the 5-LO-activating protein inhibitor MK-886 but not by the cyclooxygenase inhibitor indomethacin. Reactive oxygen species were not implicated in the mast cell-mediated toxoplasmacidal activity. The generation of LTs is important for mast cell secretion, and LTB4 released by mast cells and other inflammatory cells may be a key factor in the host defense against T. gondii.
Henderson
W R
WR
Department of Medicine, University of Washington, Seattle 98195-6523, USA.
Chi
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D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004789:Enzyme Activation; D007211:Indoles / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D015289:Leukotrienes / Q000096:biosynthesis / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000469:parasitology* / Q000502:physiology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010647:Phenyl Ethers; D051381:Rats; D017207:Rats, Sprague-Dawley; D014122:Toxoplasma / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002722:Chlorobenzenes
D000081:Acetamides; D001094:Arachidonate 5-Lipoxygenase; D007211:Indoles; D007975:Leukotriene B4; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; C060893:MK-886; D002722:Chlorobenzenes