Identification of hydroxyeicosatetraenoic acid components of schistosomal hemozoin

Carter, Melissa D.; Harry, S. Reese; Wright, David W.

doi:10.1016/j.bbrc.2007.09.051

Cited by 12 publications

(12 citation statements)

References 37 publications

(44 reference statements)

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“…The column was maintained at 40°C. Gradient elution was performed with a binary solvent system: phase A: 95% H 2 O, 5% ACN, 0.025% formic acid; phase B: 5% H 2 O, 95% ACN, 0.025% formic acid (30). The system flow rate was 0.2 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Neilson

Ren

Hong

et al. 2012

Nutrition and Cancer

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The balance of putative pro- and anti-inflammatory lipoxygenase (LOX)-derived S-hydroxyeicosatetraenoic acids (S-HETEs) in colon mucosa is a potential target for modulating colon cancer risk and progression. The biological effects of S-HETEs and R-HETEs (produced by distinct pathways) may differ, but levels of these compounds in colon are unknown. The objective of this study was to develop chiral methods to characterize HETE enantiomers in colonic mucosa and evaluate the effects of fish oil on HETE formation. C57BL/6 mice (COX-1 null, COX-2 null, wild-type) were fed a diet supplemented with either olive oil or menhaden oil for 11 weeks, and R/S-HETEs in colonic mucosa were quantified by chiral LC-MS/MS. The R-enantiomer comprised 60-72% of 5-HETE, 18-58% of 15-HETE and 1-16% of 12-HETE in colonic mucosa, suggesting that non-LOX sources contribute to HETE profiles. Fish oil reduced levels of both R- and S-HETEs, and increased the preponderance of the R-enantiomers (particularly 12- and 15-HETEs). There was apparent shunting of arachidonic acid to12/15-LOX in the COX-1 null animals. This is the first report of the enantiomeric composition of HETEs in the colon in vivo.

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Section: Methodsmentioning

confidence: 99%

Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Neilson

Ren

Hong

et al. 2012

Nutrition and Cancer

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“…The idea that SjHz may affect a different cell type(s) is supported by observations using SmHz that affected the capacity of the mouse Raw264.7 phagocytic cell line to produce nitric oxide (Carter et al 2007).…”

Section: Discussionmentioning

confidence: 97%

“…Thirdly, the purification protocol may have also have affected the SjHz immunomodulatory effects since the SjHz used is relatively crude (Carter et al 2007) compared to the extensively purified PfHz (Coban et al 2002). The PfHz purification procedure may remove attached lipid proteins, changing the architecture of native Hz and thereby inhibiting the formation of lipid derivatives important in immunomodulation.…”

Section: Discussionmentioning

confidence: 98%

“…Forty-two days post-infection with S. japonicum cercarie, SjHz was purified from adult female worms harvested from rabbits by mesenteric perfusion and then homogenized in phosphate buffered saline (PBS, pH7.4) (Carter et al 2007). Homogenates were then centrifuged twice at 1,000×g for 1 min, and the supernatants were harvested.…”

Section: Preparation Of Native Sjhzmentioning

confidence: 99%

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Hemozoin from Schistosoma japonicum does not affect murine myeloid dendritic cell function

et al. 2010

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Hemozoin (Hz) formation is a byproduct of hemoglobin digestion in some hematophagous organisms. Although Hz produced by Plasmodium falciparum (PfHz) has been shown to affect development and activities of human dendritic cells (DCs), the effects of Schistosoma Hz on DCs have not been elucidated. Our data presented in this report demonstrated that native Schistosoma japonica Hz (SjHz) did not affect the differentiation of murine bone marrow cells into immature DCs (imDCs). Maturation and stimulatory activities to T cells by imDCs induced by LPS were not altered in the presence of SjHz; whereas purified PfHz induced a slight increase in CD40 expression and enhanced IL-12p40 secretion. Lastly, SjHz treatment did not significantly affect the phagocytic activities of DCs. These data suggested that SjHz failed to exert any significant effects on the development and activities of murine myeloid DCs. The mechanisms of different effects on DCs by SjHz and PfHz remain to be elucidated.

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“…Once consumed by macrophages or dendritic cells, this apparently inert crystalline substance has been shown to exert a number of immunosuppressive as well as some proinflammatory effects in vitro and in vivo (14)(15)(16). Whether Schistosoma hemozoin has similar robust immunomodulatory effects is not yet clear (17,18). However, analyses of its effects on alternative macrophage activation and function are likely to be important in understanding both the regulation of immunopathogenesis and the apparently immuno-protective role of this cell population during chronic schistosomiasis.…”

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confidence: 99%

Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion

et al. 2013

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bThe trematode Schistosoma mansoni is one of the etiological agents of schistosomiasis, a key neglected tropical disease responsible for an estimated annual loss of 70 million disability-adjusted life years. Hematophagy represents the primary nutrient acquisition pathway of this parasite, but digestion of hemoglobin also liberates toxic heme. Schistosomes detoxify heme via crystallization into hemozoin, which is subsequently regurgitated into the host's circulation. Here we demonstrate that during experimental schistosomiasis, hemozoin accumulating in the mouse liver is taken up by phagocytes at a time coincident with the development of the egg-induced T-helper 2 (Th2) granulomatous immune response. Furthermore, the uptake of hemozoin also coincides with the hepatic expression of markers of alternative macrophage activation. Alternatively activated macrophages are a key effector cell population associated with protection against schistosomiasis, making hemozoin well placed to play an important immunomodulatory role in this disease. To systematically explore this hypothesis, S. mansoni hemozoin was purified and added to in vitro bone marrow-derived macrophage cultures concurrently exposed to cytokines chosen to reflect the shifting state of macrophage activation in vivo. Macrophages undergoing interleukin-4 (IL-4)-induced alternative activation in the presence of hemozoin developed a phenotype specifically lacking in Retnla, a characteristic alternatively activated macrophage product associated with regulation of Th2 inflammatory responses. As such, in addition to its important detoxification role during hematophagy, we propose that schistosome hemozoin also provides a potent immunomodulatory function in the coevolved network of host-parasite relationships during schistosomiasis.

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Identification of hydroxyeicosatetraenoic acid components of schistosomal hemozoin

Cited by 12 publications

References 37 publications

Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Effect of Fish Oil on Levels ofR- andS-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa

Hemozoin from Schistosoma japonicum does not affect murine myeloid dendritic cell function

Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion

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