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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The susceptibility of the human malaria parasite, Plasmodium falciparum, to killing in vitro by macrophage secretory products was investigated. The effect of O2 radicals and tumor necrosis factor on parasite viability was assessed both morphologically and by following the uptake of [3H]hypoxanthine. H2O2 produced by the interaction of glucose and glucose oxidase was found to reduce viability; this effect was reversed by the addition of exogenous catalase. Further studies indicated that the catalase level within the erythrocyte was not altered upon parasite invasion. O2 radicals produced during the xanthine-xanthine oxidase interaction also killed P. falciparum. The addition of various O2 radical scavengers (including catalase) did not reverse this effect; therefore, it was not possible to determine which of the O2 radicals were involved in the killing process. Samples from three different sources containing tumor necrosis factor, a nonspecific soluble mediator derived from Mycobacterium bovis BCG-activated macrophages treated with endotoxin, also killed the parasite. There was no evidence that tumor necrosis factor or the products of the xanthine-xanthine oxidase interaction caused damage to the erythrocyte membrane that could be implicated as an important aspect of the killing process. These findings all strongly suggest that such macrophage products play an important role in immunity to malaria.
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PMID:Killing of human malaria parasites by macrophage secretory products. 636 96

The effect of normal human peripheral blood polymorphonuclear leucocytes on in vitro multiplication of Plasmodium falciparum malaria parasites was investigated. It was shown that normal neutrophils were able to phagocytose parasitized erythrocytes and free parasites and thus inhibit in vitro multiplication of the parasite. Stimulation of the neutrophils by phorbol myristate acetate, a potent stimulus of leucocyte oxidative metabolism, resulted in enhanced inhibition of parasite growth. Superoxide dismutase, scavenger of superoxide anion, catalase, inhibitor of hydrogen peroxide, and sodium azide, inhibitor of myeloperoxidase, did not abrogate the inhibitory ability of the neutrophils. The results indicate that polymorphonuclear leucocytes play an important role in the defence against P. falciparum malaria.
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PMID:Enhanced inhibition of in vitro multiplication of Plasmodium falciparum by stimulated human polymorphonuclear leucocytes. 638 Aug 30

Previous investigations on the mechanism by which the host mounts an immune response against the human malaria parasite Plasmodium falciparum have not resolved whether cell-mediated responses, in the absence of circulating anti-Plasmodial antibodies, can effect the destruction of the intraerythrocytic parasite. We report that the intraerythrocytic parasite P. falciparum is lethally susceptible to the imposition of oxygen-dependent and oxygen-independent factor(s) released by interferon-gamma-activated, monocyte-derived human macrophages. In addition, trophozoite-schizont stage intraerythrocytic parasites were killed on exposure to small amounts of H2O2 generated in cell-free enzyme assays. Although parasiticidal activity was markedly enhanced by the addition of lactoperoxidase and KI, killing was abrogated by the addition of catalase. The ability of freshly isolated human monocytes, monocyte-derived macrophages (MDM), and lymphokine-activated MDM to kill or inhibit the growth and multiplication of the malaria parasites was assessed. Parasites were killed when exposed to monocytes or lymphokine-activated MDM, but not when exposed to nonactivated macrophages. The capacity to activate MDM for microbicidal activity was abrogated on neutralization of crude lymphokines or recombinant interferon-gamma with a monoclonal antibody prepared against interferon-gamma. The intraerythrocytic parasites surviving the cytotoxicity assay were inhibited in their development and appeared to be degenerating, a characteristic of "crisis" forms. Killing of P. falciparum correlated positively with the magnitude of the oxidative response, as evidenced by the reduction of nitroblue tetrazolium to formazan in the mononuclear phagocytes, and by the detection of secreted H2O2. Of particular interest was the observation that only the later developing stage of the intracellular parasite triggered the respiratory burst in the absence of antibody. A role for oxygen-independent parasiticidal factors was suggested by the finding that lymphokine-activated macrophages from a patient with chronic granulomatous disease were able to partially inhibit the growth of P. falciparum, although oxidative metabolism in these cells was impaired.
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PMID:Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages. 643 Oct 3

The capacity of macrophages activated in vivo and in vitro to kill Plasmodium yoelii was investigated. Macrophages activated by BCG-, Con A-, or malaria-induced lymphokines (LK) were cultured with P. yoelii-parasitized erythrocytes (PE). In some experiments, effector and target cells were separated by a 0.45-micron filter. Parasite viability was assessed a) in vivo by injection of mice and quantitative detection of parasites by RIA or b) in vitro by the incorporation of 3H amino acids into parasite proteins. Activated macrophages killed target PE in a dose-dependent manner by elaborating a membrane-permeable soluble factor(s). The addition of small amounts of immune serum augmented the killing of the parasites. LK-activated macrophages underwent an oxidative burst upon the phagocytosis of PE as evidenced by the accumulation of reduced formazan in the NBT assay. The magnitude of the oxidative response corresponded to the number of parasites that were ingested. The phagocytosis-induced oxidative burst was necessary for subsequent killing of Plasmodium. Parasites incubated in microchambers separated from macrophages by a 0.45-micron filter were susceptible to H2O2 released by LK-activated macrophages incubated with PMA, opsonized zymosan, or P. yoelii antigen. Inhibition of protein synthesis by parasites exposed to products of activated macrophages was abrogated by preincubating macrophages with catalase but not with SOD, mannitol, or histidine. These results suggest that phagocytosis-associated oxidative mechanisms mediate the destruction of the malaria parasite. Hence, cell-mediated as well as antibody-dependent mechanisms cooperate in the immune response against malaria.
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PMID:Oxidative killing of the intraerythrocytic malaria parasite Plasmodium yoelii by activated macrophages. 669 Jun 6

Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4-5.5, 37 degrees C) human red blood cell lysates were used to simulate this process, measuring the denaturation of hemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non-heme iron were observed upon lysate acidification, its rate decreasing with increasing pH, and increasing in presence of protease. Although the pH- and proteolysis-dependent release of iron paralleled Hb denaturation, released iron accounted for only a few percent of degraded Hb. Superoxide dismutase, catalase, and various scavengers of oxidative radicals had no effect on either process, consistent with the involvement of Fe(IV) intermediates in iron release from heme. Histidine and imidazole inhibited iron release, probably by binding directly to heme. Ascorbate enhanced iron release considerably but marginally enhanced the denaturation of Hb, suggesting that redox cycling of lysate free iron accelerated further release from heme. These processes could account for the endogenous supply of iron to the malarial parasite.
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PMID:Hemoglobin denaturation and iron release in acidified red blood cell lysate--a possible source of iron for intraerythrocytic malaria parasites. 822 82

Oxidative radicals are demonstrably produced in malaria-infected erythrocytes. In order to verify the biochemical origin of these radicals, erythrocyte lysate was brought to acid pH to mimic the environment of the parasite food vacuole into which host cell cytosol is transferred during parasite feeding. Oxyhemoglobin, but not deoxyhemoglobin, is rapidly converted to methemoglobin at rates which decline with increasing pH. The rate of conversion is further increased in the presence of the catalase inhibitor 3-amino-1,2,4-triazole (3-AT) and the extent of inhibition of the lysate catalase increases upon acidification, implying that H2O2 is thus produced by the spontaneous dismutation of superoxide radicals generated during methemoglobin formation. Intact Plasmodium falciparum trophozoite-infected human red blood cells (TRBC) were shown to produce H2O2 and OH radicals about twice as much as normal erythrocytes, as evidenced by the inhibition of endogenous catalase activity in the presence of 3-AT and the degradation of deoxyribose, respectively. Increased H2O2 levels and catalase activity were found in both host cell and parasite compartments. No increase in H2O2 production over that observed in uninfected erythrocytes could be detected at the ring stage when host cell digestion is absent. H2O2 and OH radicals production in TRBC was considerably reduced when digestion of host cell cytosol was inhibited either by antiproteases (which reduce the proteolysis of imported catalase) or by its alkalinization with NH4Cl (which reduce methemoglobin formation). These results suggest that reactive oxygen species are produced in the parasite's food vacuole during the digestion of host cell cytosol, and are able to egress from the parasite to the host cell compartment.
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PMID:Origin of reactive oxygen species in erythrocytes infected with Plasmodium falciparum. 826 27

Sudden episodes of massive hemolysis have become the most common cause of death among captive black rhinoceroses, and there is evidence that they occur in the wild as well. We have observed radically unique enzyme and metabolite profiles in normal rhinoceros erythrocytes compared to humans and other mammals, including marked deficiencies of intracellular adenosine triphosphate (ATP), catalase, adenosine deaminase, and other enzymes involved in glycolysis, glutathione cycling, and nucleotide metabolism. Minimal concentrations of ATP appear to impair effective acceleration of hexosemonophosphate shunt activity in response to oxidants by restricting substrate generation at the hexokinase step. Antioxidant defenses are further compromised by catalase deficiency, which may be a general characteristic of rhinoceros erythrocytes, perhaps related to the common occurrence of severe mucocutaneous ulcerative disease. It is proposed that erythrocyte ATP deficiency in rhinoceroses may be an evolutionary adaptation conferring selective advantage against common hemic parasites, comparable to the role of human glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in falciparum malaria.
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PMID:Acute episodic hemolysis in the African black rhinoceros as an analogue of human glucose-6-phosphate dehydrogenase deficiency. 841 95

Cell-cell interactions are important in intravascular inflammation. Neutrophils and monocytes adhere to the vascular endothelium and release mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and reactive oxygen species. Red blood cells (RBC) from patients with malaria, sickle cell anemia, and diabetes also adhere to endothelial cells. The objectives of this investigation were to develop a bovine system of RBC adhesion to endothelial cells and to begin to investigate the mechanisms involved in the RBC adhesion. We show that 51Cr-RBC adhere to bovine pulmonary artery endothelial cells (BPAEC) after stimulation of both cell types with endotoxin (ETX; 50 micrograms/ml). RBC adhesion to BPAEC depended on the ETX concentration and the presence of divalent cations. TNF-alpha, IL-1 beta, and antioxidants (superoxide dismutase; catalase; and dimethyl sulfoxide) all induced RBC adhesion to BPAEC. Phosphatidylserine, which has been implicated in adhesion of sickle cells and aged RBC to endothelium, reduced RBC adhesion to BPAEC, whether ETX-treated or not. In conclusion, ETX, proinflammatory cytokines and, surprisingly, antioxidants increase RBC adherence to BPAEC monolayers. RBC adhesion to endothelium is decreased by phosphatidylserine.
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PMID:Endotoxin-induced adhesion of red blood cells to pulmonary artery endothelial cells. 877 24

The various mechanisms involved in the redox defence of normal erythrocytes are adequately known. They are herein briefly reviewed, outlining the principal enzymes and metabolic pathways, such as superoxide dismutase, catalase, glutathione peroxidase and reductase, the hexose monophosphate shunt (HMS) and glutathione synthesis and turnover. The intraerythrocytic malaria parasite is imposing an oxidative stress on its host cell. Malaria infected cells produce O2-, H2O2, enhance lipide peroxidation and activate host cell HMS. This stress is produced during the digestion of host cell hemoglobin by the parasite. Hence, both parasite and host cell must be able to confront this stress. The antioxidant defence systems of the parasite and the response of those systems in the infected host cell are reviewed, underscoring unresolved problems. Nothing is virtually known on the parasite's glutathione metabolism, and on possible interactions between host cell and parasite antioxidant defence systems. The postulate that 1. host cell activated HMS in conjunction with purine salvage can provide purine nucleotides to the parasite, and 2. that glutathione transferase can participate in parasite resistance to antimalarial drugs, are also discussed.
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PMID:The redox status of malaria-infected erythrocytes: an overview with an emphasis on unresolved problems. 914 Apr 69

Reactive oxygen species are important mediators of tissue injury during malaria infection. The status of hepatic oxidative stress and antioxidant defence indices were studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and chloroquine/ polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly ICLC) treatment of infected mice. P. y. nigeriensis infection resulted in a significant increase in oxidative stress indices viz., xanthine oxidase and rate of lipid peroxidation (LPO). This was accompanied by a highly significant increase in antioxidant defence indices viz., reduced glutathione (GSH) and glutathione reductase while superoxide dismutase (SOD) and catalase showed a highly significant decrease with respect to normal mice. Chloroquine treatment of infected mice caused a decrease in parasitaemia which was associated with restoration of indices altered during infection towards normalization. Poly ICLC treatment of infected mice caused no change in blood parasitaemia but resulted in a significant increase in GSH, glutathione reductase, SOD and catalase with respect to infected mice. Combination therapy of chloroquine and poly ICLC resulted in clearance of parasitaemia and restoration of all oxidative stress and antioxidant defence indices to normal levels.
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PMID:Studies on hepatic oxidative stress and antioxidant defence system during chloroquine/poly ICLC treatment of Plasmodium yoelii nigeriensis infected mice. 1039 Nov 38


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