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PMID: 7964451 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

The Journal of experimental medicine ·Vol. 180 ·No. 5 ·1994-11-01 ·Pages 1637-48

Yong EC, Chi EY, Henderson WR

Abstract

Toxoplasma gondii tachyzoites markedly alter the profile of eicosanoids released by human mononuclear phagocytes. Freshly isolated, 2-h adherent human monocytes release both cyclooxygenase (e.g., thromboxane [TX] B2, prostaglandin [PG] E2) and 5-lipoxygenase (e.g., leukotriene [LT] B4, LTC4) products of arachidonic acid metabolism after stimulation by the calcium ionophore A23187 or ingestion of opsonized zymosan particles or heat-killed T. gondii. However, after incubation with viable T. gondii, normal and chronic granulomatous disease monocytes release only the cyclooxygenase products TXB2 and PGE2 and fail to form LTB4, LTC4, or other 5-lipoxygenase products. Monocytes maintained in culture for 5 d lose this capacity to release TXB2 and PGE2 after incubation with T. gondii. T. gondii significantly inhibit calcium ionophore A23187-induced LTB4 release by monocyte-derived macrophages; heat-killed organisms do not affect this calcium ionophore A23187-induced release of LTB4. T. gondii-induced inhibition of LTB4 release by calcium ionophore A23187-stimulated monocyte-derived macrophage is reversed by interferon (IFN)-gamma treatment of the monolayers. LTB4 induced extensive damage to the cellular membranes and cytoplasmic contents of the organisms as observed by transmission electron microscopy. Exogenous LTB4 (10(-6) M) induced intracellular killing of ingested T. gondii by non-IFN-gamma-treated monocyte-derived macrophages. IFN-gamma-induced antitoxoplasma activity in monocyte-derived macrophages was inhibited by the selective 5-lipoxygenase inhibitor zileuton but not by the cyclooxygenase inhibitor indomethacin. These findings suggest a novel role for 5-lipoxygenase arachidonic acid products in human macrophage IFN-gamma-induced antitoxoplasma activity.

MeSH Terms
Adult Animals Arachidonate 5-Lipoxygenase/physiology Arachidonic Acid/metabolism Calcimycin/pharmacology Eicosanoids/metabolism Humans Interferon-gamma/pharmacology Leukotrienes/physiology Macrophages/drug effects,physiology Monocytes/drug effects,physiology Rabbits Toxoplasma/physiology
Chemicals
Eicosanoids Leukotrienes Arachidonic Acid Calcimycin Interferon-gamma Arachidonate 5-Lipoxygenase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yong E C
Department of Medicine, University of Washington, Seattle 98195.
Chi E Y
Henderson W R
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.180.5.1637
Published
1994-11-01
Pages
1637-48
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191730
Subset
IM
Grants
NIAID NIH HHS · AI-17758 · United States
NIAID NIH HHS · AI-23713 · United States
NIAID NIH HHS · AI-34578 · United States
External Links
PubMed source DOI: 10.1084/jem.180.5.1637 PMC Full Text View journal details
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