Serum levels of eosinophil cationic protein, eosinophil-derived neurotoxin and myeloperoxidase in infections with filariea and schistosomes

Tischendorf, F. W.; Brattig, Norbert W.; Büttner, Dietrich W.; Pieper, A.; Lintzel, M.

doi:10.1016/s0001-706x(96)00038-1

Cited by 41 publications

(48 citation statements)

References 35 publications

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“…This finding was surprising, because we anticipated from existing evidence in bacterial (20) and fungal (16) infections that high MPO levels would contribute to parasite elimination. As mentioned before, high MPO plasma levels had been shown in patients with P. falciparum infection (26)(27)(28). Correspondingly, in the P. yoelii 17NL model applied here, MPO plasma levels were also significantly increased during infection.…”

Section: Discussionsupporting

confidence: 81%

“…Additionally, leukocyte-derived ROS (25) may contribute to parasite killing. Moreover, patients with P. falciparum malaria have increased MPO plasma levels (26)(27)(28), which are higher than levels observed in patients with cardiovascular disease or sepsis (28,29), for which MPO has been intensively studied in recent years. Based on these findings, we hypothesized that increased MPO production would lead to increased ROS levels, which would contribute to accelerated Plasmodium parasite clearance.…”

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confidence: 99%

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Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection

et al. 2017

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Myeloperoxidase (MPO), a leukocyte-derived enzyme mainly secreted by activated neutrophils, is known to be involved in the immune response during bacterial and fungal infection and inflammatory diseases. Nevertheless, the role of MPO in a parasitic disease like malaria is unknown. We hypothesized that MPO contributes to parasite clearance. To address this hypothesis, we used Plasmodium yoelii nonlethal infection in wild-type and MPO-deficient mice as a murine malaria model. We detected high MPO plasma levels in wild-type mice with Plasmodium yoelii infection. Unexpectedly, infected MPO-deficient mice did not show increased parasite loads but were able to clear the infection more rapidly than wild-type mice. Additionally, the presence of neutrophils at the onset of infection seemed not to be essential for the control of the parasitemia. The effect of decreased parasite levels in MPO-deficient mice was absent from animals lacking mature T and B cells, indicating that this effect is most likely dependent on adaptive immune response mechanisms. Indeed, we observed increased gamma interferon and tumor necrosis factor alpha production by T cells in infected MPO-deficient mice. Together, these results suggest that MPO modulates the adaptive immune response during malaria infection, leading to an attenuated parasite clearance.KEYWORDS peroxidase, Plasmodium, neutrophils, malaria, immunology, cytokines, animal disease model, knockout mice, T-lymphocytes, T-cell immunity, innate immunity P lasmodium falciparum infection is still one of the major tropical infectious diseases. The control of the symptomatic blood-stage infection by the host requires the innate and the adaptive immune systems (1, 2). Using mouse models, it was shown that macrophages (3), CD4 ϩ T cells (4-6), and B cells (7,8) are essential for effective parasite clearance. However, an effective immune activation and regulation is necessary for rapid parasite control and for the prevention of host pathology (5, 9). Myeloperoxidase (MPO), a heme protein secreted mainly by neutrophils, could be an important mediator in both antiparasitic defense and host pathology. Being 5% of the total protein, MPO is the most abundant protein in neutrophils (10). During infections and inflammatory diseases, MPO is increasingly released from azurophilic granules of activated neutrophils into the phagocytic vacuoles and extracellular space (11). MPO has also been found in monocytes, where it represents about 1% of the total protein (12). Monocytes later lose their ability to secret MPO during their differentiation toward macrophages. Macrophages, however, are able to take up MPO by neutrophils or MPO alone (13). The most prominent feature of MPO is its ability to catalyze the oxidation of halogenides and various substrates together with its cofactor, hydrogen peroxide (14, 15). Besides

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Section: Discussionsupporting

confidence: 81%

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confidence: 99%

Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection

et al. 2017

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“…Although the differential secretion of EDN and MBP has not been noted previously, there is precedence for the differential secretion of eosinophil granule proteins in bacterial and viral infections (19). EDN levels measured in other parasitic diseases seem to correlate with the number of peripheral blood eosinophils (38). Further, EDN, as an RNase, may be initially consumed during the migration of eosinophils into tissues and initial killing of microfilariae, accounting for its decline within the first few days after treatment.…”

Section: Discussionmentioning

confidence: 90%

Perturbations in Eosinophil Homeostasis following Treatment of Lymphatic Filariasis

Gopinath

Hanna²,

Kumaraswami³

et al. 2000

Infect Immun

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Treatment of patients with patent Wuchereria bancrofti infection results in an acute clinical reaction and peripheral eosinophilia. To investigate the dynamics of the eosinophil response, changes in eosinophil activation and degranulation and plasma levels of eosinophil-active chemokines and cytokines were studied in 15 microfilaremic individuals in south India by sequential blood sampling before and after administration of 300 mg of diethylcarbamazine (DEC). Clinical symptoms occurred within 24 h. Plasma interleukin-5 (IL-5) and RANTES levels peaked 1 to 2 days posttreatment, preceding a peak peripheral eosinophil count at day 4. Major basic protein secretion from eosinophils paralleled IL-5 secretion, while levels of eosinophil-derived neurotoxin peaked at day 13 after treatment. Expression of the activation markers HLA-DR and CD25 on eosinophils rose markedly immediately after treatment, while expression of VLA-4 and ␣4␤7 showed an early peak within 24 h and a second peak at day 13. Thus, the posttreatment reactions seen in filarial infections can be divided into an early phase with killing of microfilariae, clinical symptomatology, increases in plasma IL-5 and RANTES levels, and eosinophil activation and degranulation and a later phase with expression of surface integrins on eosinophils, recruitment of eosinophils from the bone marrow to tissues, and clearance of parasite antigen.

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“…Filaricidal activities, however, are not equivalent among the effector proteins: per mole, ECP has greater in vitro microfilarial toxicity against B. malayi than EDN (11), and MBP has been shown to have the greatest helminthotoxic activity of the eosinophilic granular proteins, due to its higher abundance in the granules than the other granular proteins (1,11). In one of the few studies of filarial infections and eosinophilic granular proteins published, both ECP and EDN levels in serum were found to be significantly higher in patients with bancroftian filariasis and onchocerciasis than in a control group from an area where the diseases were not endemic and without filarial disease (33). In our study, where the lymphatic filariasis control group was much smaller, there was no such difference in the levels of the eosinophilic granular proteins in the sera compared with a healthy control group; however, it is noteworthy that the healthy control group in our study lived in an area where filariasis is endemic.…”

Section: Discussionmentioning

confidence: 93%

“…Eosinophilic granular proteins are helminthotoxic in vitro (11) and are elevated in filarial infections (33,34). Filaricidal activities, however, are not equivalent among the effector proteins: per mole, ECP has greater in vitro microfilarial toxicity against B. malayi than EDN (11), and MBP has been shown to have the greatest helminthotoxic activity of the eosinophilic granular proteins, due to its higher abundance in the granules than the other granular proteins (1,11).…”

Section: Discussionmentioning

confidence: 99%

Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

et al. 2003

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To explore the mechanisms underlying the eosinophil-mediated inflammation of tropical pulmonary eosinophilia (TPE), bronchoalveolar lavage (BAL) fluid, serum, and supernatants from pulmonary and blood leukocytes (WBC) from patients with acute TPE (n ‫؍‬ 6) were compared with those obtained from healthy uninfected individuals (n ‫؍‬ 4) and from patients with asthma (n ‫؍‬ 4) or elephantiasis (n ‫؍‬ 5). Although there were no significant differences in the levels of interleukin-4 (IL-4), IL-5, IL-13, eotaxin, granulocyte-macrophage colony-stimulating factor, RANTES, or eosinophil cationic protein, there was a marked increase in eosinophil-derived neurotoxin (EDN) both systemically and in the lungs of individuals with TPE compared to each of the control groups (P < 0.02). Moreover, there was a compartmentalization of this response, with EDN levels being higher in the BAL fluid than in the serum (P < 0.02). Supernatants from WBC from either whole blood or BAL cells were examined for chemokines, cytokines, eosinophil degranulation products, and arachidonic acid metabolites. Of the many mediators examined-particularly those associated with eosinophil trafficking-only EDN (in BAL fluid and WBC) and MIP-1␣ (in WBC) levels were higher for TPE patients than for the non-TPE control groups (P < 0.02). These data suggest it is the eosinophilic granular protein EDN, an RNase capable of damaging the lung epithelium, that plays the most important role in the pathogenesis of TPE.Tropical pulmonary eosinophilia (TPE), an unusual manifestation of human lymphatic filarial infection, is characterized by an eosinophilic pulmonary inflammatory infiltrate and marked elevations of immunoglobulin E (IgE) and circulating eosinophils in the serum, all felt to be mediated by immunologic hyperreactivity to filarial parasites or their antigens. Although 129 million people worldwide are infected with lymphatic filariasis, Ͻ0.01% develop TPE (20). It is unclear what factors predispose patients to the rare, localized, and profound immune dysregulation associated with TPE.

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Serum levels of eosinophil cationic protein, eosinophil-derived neurotoxin and myeloperoxidase in infections with filariea and schistosomes

Cited by 41 publications

References 35 publications

Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection

Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection

Perturbations in Eosinophil Homeostasis following Treatment of Lymphatic Filariasis

Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

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