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. 1992 Jun;76(2):242–250.

Entamoeba histolytica alters arachidonic acid metabolism in macrophages in vitro and in vivo.

W Wang 1, K Chadee 1
PMCID: PMC1421539  PMID: 1634248

Abstract

Entamoeba histolytica infections are associated with a state of transient suppression of cell-mediated immunity. Macrophages, the most important cells in host defence and control of invasive amoebiasis, in infected animals have been found to be deficient in effector functions and accessory cell potential. However, little is known of the cellular mechanisms responsible for the down-regulation. This study investigated whether macrophage dysfunction in amoebiasis is associated with altered macrophage arachidonic acid (AA) metabolism. Resident peritoneal macrophages (PMO) from naive gerbils produced enhanced levels of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) in response to live E. histolytica trophozoites, to diffusible excretory/secretory products released from live amoebae in millicells and to freeze-thawed soluble amoebic proteins that were inhibitable by indomethacin (INDO) and nordihydroguaiaretic acid (NDGA), respectively. In contrast to PMO from naive gerbils, PMO from animals with amoebic liver abscesses at 10, 20 and 30 days post-infection (p.i.) released high basal levels of PGE2 and LTC4. In response to zymosan stimulation, PMO from infected animals produced two- and fourfold less PGE2 and LTC4, respectively, as compared to uninfected controls. AMO showed high constitutive basal release of PGE2 and LTC4. In response to amoebic and zymosan stimulation, AMO at 10 days p.i. produced significantly higher levels of PGE2 than AMO at 20 days p.i., while AMO at 30 days p.i. were refractory to stimulation to produce higher than basal levels of PGE2. Early (10 days) and late (20-30 days) AMO were refractory to amoebic and zymosan stimulation for enhanced LTC4 release. Pretreatment of AMO with AA substrate restored optimal PGE2 and LTC4 biosynthesis, but the cells were generally unresponsive to zymosan stimulation to produce augmented levels of LTC4. These results strongly suggest that intrinsic or secreted products or both from E. histolytica can induce profound alteration of eicosanoid formation in cyclooxygenase and lipoxygenase pathways in macrophages from naive and infected animals and that AA metabolism by AMO is sequentially modified during the course of the disease.

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Selected References

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