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

The profound changes in the morphology, antigenicity, and functional properties of the host erythrocyte membrane induced by intraerythrocytic parasites of the human malaria Plasmodium falciparum are poorly understood at the molecular level. We have used mouse mAbs to identify a very large malarial protein (Mr approximately 300,000) that is exported from the parasite and deposited on the cytoplasmic face of the erythrocyte membrane. This protein is denoted P. falciparum erythrocyte membrane protein 2 (Pf EMP 2). The mAbs did not react with the surface of intact infected erythrocytes, nor was Pf EMP 2 accessible to exogenous proteases or lactoperoxidase-catalyzed radioiodination of intact cells. The mAbs also had no effect on in vitro cytoadherence of infected cells to the C32 amelanotic melanoma cell line. These properties distinguish Pf EMP 2 from Pf EMP 1, the cell surface malarial protein of similar size that is associated with the cytoadherent property of P. falciparum-infected erythrocytes. The mAbs did not react with Pf EMP 1. In one strain of parasite there was a significant difference in relative mobility of the 125I-surface-labeled Pf EMP 1 and the biosynthetically labeled Pf EMP 2, further distinguishing these proteins. By cryo-thin-section immunoelectron microscopy we identified organelles involved in the transit of Pf EMP through the erythrocyte cytoplasm to the internal face of the erythrocyte membrane where the protein is associated with electron-dense material under knobs. These results show that the intraerythrocytic malaria parasite has evolved a novel system for transporting malarial proteins beyond its own plasma membrane, through a vacuolar membrane and the host erythrocyte cytoplasm to the erythrocyte membrane, where they become membrane bound and presumably alter the properties of this membrane to the parasite's advantage.
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PMID:Transport of an Mr approximately 300,000 Plasmodium falciparum protein (Pf EMP 2) from the intraerythrocytic asexual parasite to the cytoplasmic face of the host cell membrane. 243 28

The asynchronously developing malaria parasite Plasmodium berghei was synchronized using in vitro cultivation techniques (Mons et al. 1985). After the infection of naive mice, preparations of parasitized erythrocytes with a high level of synchronism could be obtained. Immunofluorescence and immunoblotting techniques using serum from immunized mice were applied to determine stage-specific immunogenic molecules in the parasitized erythrocyte preparations. These techniques allowed the detection of not only parasite-derived but also altered-self molecules. Membrane fluorescence of infected erythrocytes was detected only in preparations containing late trophozoites and schizonts. The appearance of this fluorescence pattern coincided with the presence of immunogenic polypeptides of mol. wt. greater than 200 kD, 86 kD, and 56 kD especially, among some other polypeptides. Preliminary experiments using lactoperoxidase-catalyzed radioiodination suggested that the greater than 200 kD and 56 kD molecules were present at the erythrocyte surface. One molecule with mol. wt. 153 kD was associated with the presence of ring-infected erythrocytes. However, membrane fluorescence of ring-stage-infected erythrocytes was not found. Noninfected erythrocytes sometimes showed membrane fluorescence.
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PMID:Stage-specific proteins of Plasmodium berghei-infected red blood cells detected by antibodies of immune mouse serum. 306 Aug 73

Vaccination trials have shown that a purified, 74 kDa glycoprotein, GP74, isolated from the host cell membrane of Plasmodium knowlesi-infected rhesus erythrocytes, can provide protective immunity against P. knowlesi malaria. We have extended this work by a tryptic peptide analysis of the disposition of GP74 in the host cell membrane. Of the 18 peptides characterized by high-performance liquid chromatography only four were accessible to lactoperoxidase-catalyzed radioiodination of non-leaky, schizont-infected host cells from the extracellular space. Metabolic labeling with radioactive glucosamine indicates that two of the surface exposed peptides are glycopeptides, and one of these, peptide 12 appears to carry a dominant antigenic site, according to its reactivity with immunoglobulin from sera of monkeys protected against P. knowlesi malaria.
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PMID:Membrane orientation and antigenic peptides of an immunoprotective 74 kDa Plasmodium knowlesi glycoprotein. 373 96

The SICA[-] or non-agglutinable phenotype of Plasmodium knowlesi schizont-infected erythrocytes has been defined serologically but not biochemically. Similarly, non-cloned SICA[+] or agglutinable parasites have been shown serologically to express SICA or variant antigen(s) but the number and nature of such antigens have not been defined. Here we describe the immunochemical analysis of surface antigen expression on [125I]lactoperoxidase-labelled erythrocytes infected either with a SICA[-] clone or with non-cloned SICA[+] parasites using the methods developed for identification of variant antigens with cloned SICA[+] parasites. No 125I-labelled antigens in the size range Mr 190 000-225 000 were specifically immunoprecipitated from erythrocytes infected with the SICA[-] clone, even using homologous antisera produced by multiple infections or immunizations. Further, no 125I-labelled proteins of this size were seen in detergent extracts of the SICA[-] parasites that were not also seen with uninfected cells. We conclude that the SICA[-]phenotype reflects the absence of a variant antigen at the erythrocyte surface, as predicted by the serological assays. In contrast, with the non-cloned SICA[+] parasites, a complex group of proteins, Mr 195 000-225 000, was identified by [125I]lactoperoxidase labelling of intact infected erythrocytes. These proteins are SICA antigens since they not only share the characteristic detergent solubility properties and size range of SICA antigens identified previously with SICA[+] clones, but they were only immunoprecipitated by antisera which reacted specifically with the surface of infected erythrocytes. Agglutinating sera immunoprecipitated several of these 125I-labelled antigens. Sera specific for clones derived from this non-cloned SICA[+] population failed to agglutinate, but did react by indirect immunofluorescence with 10-16% of infected cells. These sera specifically immunoprecipitated single, quantitatively minor 125I-labelled antigens in this size range. The results suggest that a population of non-cloned SICA[+] parasites contains at least 10 different variant-antigen phenotypes. Indirect immunofluorescence was also performed against a non-cloned SICA[+] population derived by antigenic variation of a SICA[+] clone in vivo. The variant population contained at least 3 antigenically distinct SICA phenotypes, indicating that antigenic variation of clones may produce populations as antigenically heterogenous as antigenic variation of uncloned lines. It is therefore likely that natural malaria isolates contain a large number of different variant antigens.
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PMID:Immunochemical analysis of surface membrane antigens on erythrocytes infected with non-cloned SICA[+] or cloned SICA[-] Plasmodium knowlesi. 390 20

In this report and (R. Schmidt-Ullrich, L. H. Miller, and D. F. H. Wallach. Manuscript in preparation.), we have demonstrated that malaria proteins on the surface of merozoites and infected erythrocytes cross-react between at least two primate malarias, Plasmodium knowlesi and P. falciparum. Sera from five Gambian adults who were highly immune to P. falciparum were used as a reagent to study the cross-reactivity between P. falciparum schizonts and surface proteins on P. knowlesi merozoites. Although the sera bound to the surface of viable, intact P. knowlesi merozoites, the sera did not block invasion of rhesus erythrocytes. 125I-lactoperoxidase-labeled surface proteins on merozoites formed complexes with the antibody. All major protein bands seen in the electrophoresis of the original Triton extract were bound by the immune sera. Because Gambians have never been exposed to P. knowlesi malaria, the antibodies that reacted with P. knowlesi merozoites must be directed against antigens of another parasite such as P. falciparum. We tested this hypothesis by competition for antibody in a Gambian serum between Triton-extracted antigens from P. falciparum schizont-infected erythrocytes and from surface-labeled P. knowlesi merozoites. P. falciparum inhibited the reaction, thus indicating cross-reaction between antigens in P. falciparum schizonts and P. knowlesi merozoites.
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PMID:Determinants on surface proteins of Plasmodium knowlesi merozoites common to Plasmodium falciparum schizonts. 615 61

A range of 22 mouse anti-P. falciparum monoclonal antibodies have been characterized by indirect immunofluorescence and immunoprecipitation. On the basis of these studies, 5 groups of antibodies and 6 classes of antigen were defined. Group I antibodies give, bright, uniform, generalised staining of all blood stages including gametocytes. Three of these antibodies precipitate a metabolically labelled molecule(s) of 35 kDa. One precipitates a 50 kDa antigen. Group II antibodies, which give strong localised immunofluorescence in merozoites, and a weak diffuse pattern in earlier stages, precipitate biosynthetically labelled molecules of 160 kDa. Group III antibodies react with all asexual stages. With merozoites they produce intense staining around the perimeter, both in fixed and unfixed preparations. They precipitate biosynthetic molecules of 190 kDa. Group IV antibodies are identical to Group III except they are stage restricted to schizonts and merozoites. They also precipitate 190 kDa antigens. These, however, in contrast to group III, are readily accessible to 125I-lactoperoxidase labelling. One antibody also precipitates a set of smaller peptides. Finally, Group V antibodies produce very bright ill-defined staining of pigment-containing parasites, as well as of inclusions in the red cell. They precipitate a series of molecules of 160, 60 and 35 kDa which are readily accessible to 125I. The 160 kDa molecule is also labelled by [35S]methionine. These results are discussed in the context of the development of a malaria vaccine and immunodiagnostic tests.
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PMID:Antigens of the erythrocytes stages of the human malaria parasite Plasmodium falciparum detected by monoclonal antibodies. 635 Aug 71

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

Mature asexual stages of the malaria parasite Plasmodium Knowlesi synthesize proteins of Mr 180 000-225 000 that are expressed on the outer membrane of infected erythrocytes and which vary antigenically such that different parasite clones are specifically agglutinated with homologous antibody. Other non-agglutinable clones have been prepared which fail to express variant antigen on infected cells. Two agglutinable clones of different variant antigen phenotypes and a non-agglutinable cone were examined to determine the proportion of total malarial proteins represented by variant antigens. Malarial proteins were labelled with various radioactive amino acids and the sodium dodecyl sulphate--polyacrylamide gel patterns for the three clones compared by fluorography. The patterns were indistinguishable, the variant antigens being undetectable in analyses of total malarial proteins. Furthermore, these antigens were not detected by Coomassie Blue-staining of total cellular proteins after electrophoresis. Sodium dodecyl sulphate and Triton X-100 extracts of labelled cells were immunoprecipitated using a panel of sera of defined agglutination specificity. The variant antigens could not be detected in the fluorographic patterns of total malarial antigens immunoprecipitated by these sera. In contrast, after lactoperoxidase catalysed radio-iodination of intact schizont-infected cells, the 125I-variant antigens on the cell surface were identified by demonstrating their accessibility both to antibody and to trypsin with intact cells. Thus, the variant antigens are quantitatively very minor malarial proteins that can only be detected by methods which selectively analyse the subset of proteins on the erythrocyte surface.
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PMID:Protein antigens of Plasmodium knowlesi clones of different variant antigen phenotype. 671 54

The surface proteins and glycoproteins of red cells from Plasmodium berghei-infected blood have been radio-isotope labelled and compared with those of normal mouse erythrocytes using the following protein labelling probes: lactoperoxidase-catalysed radio-iodination of tyrosyl residues, periodate oxidation and NaB3H4 reduction of sialic acid and oxidation of galactosyl/N-acetylgalactosaminyl residues by galactose oxidase with subsequent NaB3H4 reduction. During P. berghei infection, new tyrosyl-labelled proteins with apparent molecular weights (Mr) of 60 000, 54 000, 40 000 and 27 500 appeared on the surface of most, if not all, red cells in the blood. Purified multinucleate cells (mostly reticulocytes) differed only in that they also had a surface protein with Mr of 83 000. However, this molecule is thought to be specific to mouse reticulocytes rather than derived from parasites. In contrast to the relatively minor changes detected with radio-iodination, striking changes in glycoprotein radio-isotope labelling resulted from infection. All of the red cells in infected blood of greater than 20% parasitaemia lost their periodate-sensitive glycoprotein sialic acid. With some samples there was little change in glycoprotein labelling by the galactose oxidase method, provided neuraminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infminidase was also added. Modification of the exocyclic hydroxyls of sialic acid is postulated to account for this. Other blood samples exhibited a dramatic loss of galactose oxidase-dependent labelling. It is suggested that these observations may relate to the excessive red cell destruction of uninfected as well as infected cells which has been inferred in many haemosporidial infections, including malaria.
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PMID:Characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: Plasmodium berghei infections of BALB/c mice. 700