Incorporation of Arachidonic Acid by Microfilariae of Brugia malayi

Longworth, David L.; Foster, Donald W.; Dvorak, Ann M.; Weller, Peter F.

doi:10.1093/infdis/152.6.1317

Cited by 25 publications

(7 citation statements)

References 19 publications

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“…A key observation which pinpoints eicosanoids as central players in filarial infection is that microfilariae themselves secrete prostanoids, in particular prostacyclin and PGE2 (Liu, Serhan & Weller, 1990). Earlier studies had established that Mf incorporate exogenous arachidonic acid (Longworth et al 1985). When Mf were tested in the presence of DEC, parasite prostanoid production was severely inhibited (Kanesa-thasan et al 1991).…”

Section: Dec Effects On Arachidonic Acid Metabolism May Be the Primarmentioning

confidence: 99%

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Maizels¹,

Denham

1992

Parasitology

134

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Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals. It may also account for the inconsistencies in the effects of DEC against different filariae in different host species. In addition, we discuss the significant side-effects often associated with treatment of heavily infected patients, and the longer-term changes in T-cell reactivity and the host-parasite relationship which follow successful treatment with DEC.

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Section: Dec Effects On Arachidonic Acid Metabolism May Be the Primarmentioning

confidence: 99%

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Maizels¹,

Denham

1992

Parasitology

134

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“…Most parasitic helminths lack the ability to synthesize polyunsaturated fatty acids de novo (Frayha & Smyth, 1983). In microfilariae and adults of Brugia malayi , arachidonate is rapidly esterified and incorporated into phospholipids and neutral lipids (Longworth et al , 1985, 1987, 1988; Liu & Weller, 1990). In the presence of exogenous arachidonic acid, Taenia taeniaformis metacestodes may generate thromboxane (Leid & McConnell, 1983a), prostaglandins (Leid & McConnell, 1983b) and hydroxyeicosatetraenoic acid (HETE)-like compounds with chemotactic activities towards eosinophils (Potter & Leid, 1986).…”

Section: Introductionmentioning

confidence: 99%

Uptake and utilization of arachidonic acid in infective larvae ofAngiostrongylus cantonensis

Tang

Wang

2010

J. Helminthol.

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Infective larvae of Angiostrongylus cantonensis may take up and incorporate exogenous arachidonic acid into their lipid pool. By scintillation counting, uptake and incorporation were determined to be time dependent. Arachidonic acid was mainly incorporated into phospholipid (56.8%) and neutral lipid (22.4%) pools. In the neutral lipids, 64.0% was diglyceride and 36.0% triglyceride. Phosphatidylcholine was the predominant fatty acid in the phospholipid pool. In addition to the release of leukotriene B4, the parasite was found to generate radiolabelled CO2 after incubation with [U-14C]arachidonate. Moreover, enzymatic analysis of crude extracts revealed the presence of acyl-CoA dehydrogenase (short and long chain), thiolase, enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. These findings suggest that infective larvae of A. cantonensis not only take up and incorporate exogenous arachidonic acid into their lipid pool, but may also utilize the fatty acid through a functional β-oxidation pathway.

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“…Specifically, the thromboxanes (Txs) constrict blood vessels, suppress cyclic AMP, and promote platelet aggregation, while leukotrienes (LTs) are related to vascular permeability, chemotaxis, and polymorphonuclear leukocyte activation (17). Some of these lipid mediators have been observed in lymphatic filariae (10,11,13) and Onchocerca volvulus (4). Clinical studies have demonstrated high concentrations of TxB2 in the plasma of patients with septic and endotoxic shock (1) and in patients with chronic obstructive pulmonary disease (6).…”

mentioning

confidence: 99%

High Levels of Serum Thromboxane B2 Are Generated during Human Pulmonary Dirofilariosis

Morchón

López-Belmonte

Rodríguez-Barbero

et al. 2006

Clin Vaccine Immunol

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The canine parasite Dirofilaria immitis can infect humans. Patients with pulmonary dirofilariosis develop significantly higher thromboxane B2 levels than healthy individuals living in areas where dirofilariosis is endemic and in areas where dirofilariosis is not endemic. The possible role of Wolbachia bacteria in the appearance of this eicosanoid is discussed.Heartworm disease caused by Dirofilaria immitis in dogs and cats is distributed in temperate, subtropical, and tropical areas worldwide (7). The infection is transmitted by several mosquito species, most of which are able to feed on both animal reservoirs and humans. Thus, in areas of endemicity, people are at risk of infection. Human dirofilariosis is radiologically characterized by a solitary pulmonary calcified or noncalcified nodule (5, 15). These nodules appear when a migrating immature worm is trapped in a branch of the pulmonary artery and dies, causing coagulation necrosis with fibrosis and infiltration of inflammatory cells (8,16). Wolbachia symbiont bacteria are a stable and abundant component of the bodies of many filarial species (2). In human D. immitis infections, high levels of immunoglobulin G (IgG) antibodies against the Wolbachia surface protein (WSP) have consistently been detected in patients with pulmonary dirofilariosis, while in healthy donors living in areas of endemicity, the levels of IgG anti-WSP are much lower (18). In addition, Wolbachia bacteria play an important role in the immunopathogenesis of both human filarial diseases (3, 19) and animal dirofilariosis (9). Eicosanoids are lipid mediators that regulate different physiological processes and modulate inflammatory and immunological responses in mammals (4). The effects of some of these eicosanoids antagonize the effects of others. Specifically, the thromboxanes (Txs) constrict blood vessels, suppress cyclic AMP, and promote platelet aggregation, while leukotrienes (LTs) are related to vascular permeability, chemotaxis, and polymorphonuclear leukocyte activation (17). Some of these lipid mediators have been observed in lymphatic filariae (10,11,13) and Onchocerca volvulus (4). Clinical studies have demonstrated high concentrations of TxB2 in the plasma of patients with septic and endotoxic shock (1) and in patients with chronic obstructive pulmonary disease (6).The aim of this study was to investigate the levels of eicosanoids in the sera of patients with pulmonary dirofilariosis, a disease characterized by the inflammatory obstruction of pulmonary arteries and a disease in which the Wolbachia symbiont bacteria stimulate the immune systems of infected individuals.Eighty human serum samples were divided into three groups. Group 1 (G1; n ϭ 10) comprised serum samples from patients diagnosed with pulmonary dirofilariosis caused by D. immitis (these samples were kindly provided by Patrick Lammie from the Centers for Disease Control and Prevention, Atlanta, Ga.). These samples have high levels of specific IgG against WSP, as demonstrated previously (18). Group 2 (G2; n ϭ 40) compr...

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Incorporation of Arachidonic Acid by Microfilariae of Brugia malayi

Cited by 25 publications

References 19 publications

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Uptake and utilization of arachidonic acid in infective larvae ofAngiostrongylus cantonensis

High Levels of Serum Thromboxane B2 Are Generated during Human Pulmonary Dirofilariosis

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