INCREASED PRODUCTION OF ARACHIDONATE METABOLITES BY PERITONEAL CELLS OF MICE INFECTED WITH <i>PLASMODIUM VINCKEI VINCKEI</i>

Ia, Clark; Nh, Hunt

doi:10.1038/icb.1986.44

Cited by 8 publications

(3 citation statements)

References 15 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Malaria infection is known to increase the production of prostaglandins and thromboxane B2 by monocytes. 18 This increased production of prostaglandins is associated with the immunosuppression caused by malaria. 19,20 The immunosuppression induced by prostaglandins may be protective rather than detrimental in cerebral malaria.…”

mentioning

confidence: 99%

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Xiao

Patterson²,

Yang³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Because microvascular damage is a common feature of cerebral malaria, we have examined the role eicosanoid metabolites (prostaglandins and leukotrienes) in experimental cerebral malaria. Eighty ICR mice were infected with Plasmodium berghei ANKA, with 40 uninfected mice as controls. Half of the infected mice were treated on days 4 and 5 with aspirin, a prostaglandin synthesis inhibitor. Infected mice started to die of cerebral malaria on day 6, and by day 17, all infected mice died. In contrast, all infected mice treated with aspirin died by day 12. Infected mice had increased phospholipase A2 mRNA expression in the spleen and cyclooxygenase 1 (COX1) and COX2 expression in the brain. At the peak of cerebral malaria, infected mice had higher serum leukotriene B4 levels than control mice, and aspirin-treated infected mice had higher serum leukotriene B4 levels than untreated infected mice. These results suggest that prostaglandins are protective whereas leukotrienes are detrimental in cerebral malaria.Microvascular damage is a common feature of both primate and murine cerebral malaria. Humans who die of cerebral malaria caused by Plasmodium falciparum infection have petechial and ring hemorrhage and edema in the brain. [1][2][3][4][5][6] Similar findings are also seen in cerebral malaria of rhesus monkeys caused by P. coatneyi 7 and of mice caused by P. berghei ANKA. 8 The mechanisms involved in the induction of microvascular damage during cerebral malaria are not well studied. Because cerebral malaria is associated with the over-production of T helper-1 and proinflammatory cytokines (tumor necrosis factor-␣ [tnF-␣], interferon-␥ [IFN-␥], and interleukin-1 [IL-1]), 9-11 it is suggested that these cytokines cause cerebral malaria by up-regulation of intercellular adhesion molecule-1 (a cytoadhesion molecule involved in the adhesion of parasitized erythrocytes and mononuclear cells to endothelial cells) expression and nitric oxide production, which lead to mechanic blockage and disrupted neurotransmission. 11-13 However, whether endothelial blockage and activation themselves cause brain hemorrhage is not clear. The role of platelets in cerebral malaria has attracted some attention, although detailed pathways for the plateletinduced pathology have not yet been studied. 14 An alternative effect of the proinflammatory cytokines is the modulation on the production of eicosanoids (prostaglandins and leukotrienes), which are important in the maintenance of the structure and function of blood vessels. 15 Increased phospholipase A2 activities have been reported in adults infected with P. falciparum. 16 Children with cerebral malaria also have higher phospholipase A2 expression than those with uncomplicated malaria. 17 Because the expression of other enzymes such as cyclooxygenase 1 and 2 (COX1 and COX2) (for prostaglandin synthesis) and lipoxygenase (for leukotriene synthesis) in malaria infection is not known, it is not clear which eicosanoid pathway is involved in the pathogenesis. Malaria infection is known to ...

show abstract

mentioning

confidence: 99%

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Xiao

Patterson²,

Yang³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…Clark and Hunt showed that peritoneal macrophages from mice infected with murine malaria produced increased amounts of arachidonate metabolites. 1 A report of successful treatment of human cerebral malaria with prostaglandin I 2 was followed by prevention of murine cerebral malaria by a stable prostaglandin I 2 analog. 2,3 Intervention in murine malaria with aspirin, a prostaglandin synthesis inhibitor, suggested that prostaglandins are protective against cerebral malaria, while leukotrienes aggravate this disease.…”

mentioning

confidence: 99%

Short Report: Lethal Malaria in Cytosolic Phospholipase A2- And Phospholipase A2iia-Deficient Mice

Ishikawa

Uozumi²,

Shiibashi³

et al. 2004

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Lipid mediators play important roles in the pathogenesis of malaria. Phospholipase A2s are enzymes involved in the production of these mediators, and they function in inflammation. Among them, cytosolic phospholipase A2 (cPLA2) is a key enzyme in the metabolism of arachidonic acid, the first intermediate in the production of lipid mediators. Plasmodium berghei ANKA causes cerebral malaria in CL57B/6 mice, and we recently produced cPLA2-deficient mice with this background. With the expectation of reduced pathogenicity, we performed experimental infection in these mice. Unexpectedly, the infected mice developed cerebral malaria and died at the same time as the control mice, while the parasitemia progressed similarly in both groups. These observations suggest that secretory PLA2s rather than cPLA2 may be involved in the aggravation, although possible compensation by the induction of other enzymes has not been excluded. The present findings are expected to help clarify the involvement of various phospholipase A2s in malaria.

show abstract

“…Proliferation and activation of blood monocytes are important features of malaria infection (Butcher & Clancy 1984). Recent in vitro and in vivo evidence points to the participation of reactive oxygen species (ROS) in killing malaria parasites during murine and human infections (Dockrellds Playfair 1983;Ockenhouse & Shear 1984;Clark & Hunt 1986;Li & Li 1987). Increased generation of ROS has been shown in human Plasmodium jalciparum infection (Descamps-Latscha et al 1987;Nielsen & Theander 1989;Dubey et al 1991).…”

mentioning

confidence: 99%

Generation of reactive oxygen species by blood monocytes during acutePlasmodium knowlesiinfection in rhesus monkeys

Jayshree

Ganguli

Dubey

et al. 1993

Apmis

View full text Add to dashboard Cite

The status and kinetics of monocyte activation during acute P. knowlesi infection was investigated by latex‐induced, luminol‐dependent chemiluminescence (CL) response. The contribution of various reactive oxygen species (ROS) to CL response was estimated before infection and at peak parasitaemia (day 7 post infection) by using scavengers of ROS (benzoate, catalase and superoxide dismutase). The chemiluminescence index (CLI) was not found to be significantly different from controls on day 2 postinfection, but was significantly higher on days 5 and 7 postinfection. Hydroxyl radical (OH·) production was considerably elevated, whereas superoxide anion(O2−·) and hydrogen peroxide (H2O2) production dropped following infection. These changes in generation of ROS are discussed in relation to the progression of parasitaemia to high levels, immunopathology and immunosuppression during acute P. knowlesi infection.

show abstract

INCREASED PRODUCTION OF ARACHIDONATE METABOLITES BY PERITONEAL CELLS OF MICE INFECTED WITH PLASMODIUM VINCKEI VINCKEI

Cited by 8 publications

References 15 publications

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

Short Report: Lethal Malaria in Cytosolic Phospholipase A2- And Phospholipase A2iia-Deficient Mice

Generation of reactive oxygen species by blood monocytes during acutePlasmodium knowlesiinfection in rhesus monkeys

Contact Info

Product

Resources

About