Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 135-kD parasite protein, a minor component of the Plasmodium knowlesi malaria radiolabeled proteins released into culture supernatant at the time of merozoite release and reinvasion, specifically bound to human erythrocytes that are invaded and carry a Duffy blood group determinant (Fya or Fyb), but did not bind to human erythrocytes that are not invaded and do not carry a Duffy determinant (FyFy). Specific anti-Duffy antibodies blocked the binding of the 135-kD protein to erythrocytes carrying that specific Duffy determinant. Purified 135-kD protein bound specifically to the 35-45-kD Duffy glycoprotein on a blot of electrophoretically separated membrane proteins from Fya and Fyb erythrocytes but not from FyFy erythrocytes. Binding of the 135-kD protein was consistently greater to Fyb than to Fya both on the blot and on intact erythrocytes. The 135-kD protein also bound to rhesus erythrocytes that are Fyb and are invaded, but not to rabbit or guinea pig erythrocytes that are Duffy-negative and are not invaded. Cleavage of the Duffy determinant by pretreating Fyb human erythrocytes with chymotrypsin greatly reduced both invasion and binding of the 135-kD protein, whereas pretreating Fyb erythrocytes with trypsin had little effect on the Duffy antigen, the 135-kD protein binding, or on invasion. However, instances of invasion of other enzyme-treated erythrocytes that are Duffy-negative and do not bind the 135-kD protein suggest that alternative pathways for invasion do exist.
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PMID:Receptor-like specificity of a Plasmodium knowlesi malarial protein that binds to Duffy antigen ligands on erythrocytes. 283 62

The A, B, O, D, Du, C, c, E, e, M, N, S, s, Kell and Duffy antigens were determined on 190 blood samples from Hausas in the north of Nigeria. The highest gene frequencies in the rhesus system were cDe (0.648) and cde (0.176). Su gene frequency was 0.270. The great majority of subjects were Kell negative (98.9%) and Duffy negative (98.8%). As the MNSs group determinants are carried by glycophorins, which are also receptor sites for Plasmodium falciparum, and the Duffy antigen marks the receptor for P. vivax, the present study provides data of interest in the epidemiology and genetics of malaria.
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PMID:Some red cell antigens in the Hausa population of northern Nigeria. 393 Mar 87

Leukocytes migrate from the blood to sites of inflammation in response to locally produced chemoattractants that activate specific cell surface receptors. The primary structures of leukocyte receptors for N-formyl peptides, C5a, platelet-activating factor, and 8 of the 18 known human chemokines (interleukin-8 and related molecules) have been deduced from cloned cDNAs. All of these are seven-transmembrane-domain rhodopsin-like G protein-coupled receptors. Biochemical and molecular genetic analysis of the chemoattractant receptors indicates that the chemoattractants may have both broadly overlapping as well as specialized roles in the regulation of acute and chronic inflammation. Interestingly, the chemokine receptors have functional homologues in human cytomegalovirus and Herpesvirus saimiri. Moreover, the Duffy antigen, which mediates invasion of erythrocytes by Plasmodium vivax, a major cause of malaria, is also a chemokine binding protein. These surprising developments suggest that in addition to leukocyte-mediated inflammation, the chemokines may also be involved in erythrocyte function and, through molecular mimicry, in microbial pathogenesis.
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PMID:The molecular biology of leukocyte chemoattractant receptors. 801 Dec 92

Chemokines are small pro-inflammatory peptides that are best known for their leukocyte-chemoattractant activity. The cloned leukocyte chemokine receptors, interleukin 8 receptor (IL-8R) types A and B and the macrophage inflammatory protein 1 alpha (MIP-1 alpha)/RANTES receptor, are related by sequence and chemokine binding to two herpesvirus products, and to the Duffy antigen that mediates erythrocyte invasion by the malaria-causing parasite Plasmodium vivax. Here, Sunil Ahuja, Ji-Liang Gao and Philip Murphy suggest that, in addition to the activation of leukocytes, chemokines may be important in the function of erythrocytes and, through molecular mimicry, in microbial pathogenesis.
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PMID:Chemokine receptors and molecular mimicry. 806 75

Malaria is a major risk for more than two billion human beings on Earth, and is the cause of 700,000 to 2.5 million deaths per year. The causative factor, Plasmodium (four species), involves an asexual cycle in man and a sexual one in anopheline mosquitoes. The four species of Plasmodium are pathogenic for man but P. falciparum accounts for more than 90% of deaths. Only black Africans are refractory to P. vivax, a characteristic linked to the lack of Duffy antigen. Among the 400 species of anophelines so far recorded, less than 50 are recognized malaria vectors. Every one has its own geographic and ecological characteristics, which locally induce the epidemiological trends and its biodiversity. In a given site transmission depends on competent anopheline species, their infective rate and their biting rate. Inhabitants of endemic areas develop during infancy immunity which protect them during the rest of their lives. This immunity (premunition) between parasite and its host is acquired at an heavy price of infant mortality. It can decrease rapidly when people leave endemic areas. Because inhabitants of endemic areas continue to harbor asymptomatic parasites they become good parasite reservoirs. The diversity of epidemiological situations needs a diversification of malaria control measures. The prognosis of the evolution of malaria depends on control measures, applied or not, and on the evolution of climatic and anthropic environment, which are very hard to predict for the time being.
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PMID:[Vectors and environmental factors in malaria]. 1018 11

In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is alpha(+)-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that alpha(+)-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that alpha(+)-thalassemia may facilitate so-called "benign" Plasmodium vivax infection to act later in life as a "natural vaccine" against severe Plasmodium falciparum malaria. Here, in a P. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of alpha(+)-thalassemia >/=0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a-b-]) on the FY*A allele. In this study population there were 23 heterozygous and no homozygous individuals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous (FY*A/FY*A(null)) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.163) compared with FY*A/FY*A(null) (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47-8.91). Emergence of FY*A(null) in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise alpha(+)-thalassemia/P. vivax-mediated protection against severe P. falciparum malaria.
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PMID:Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea. 1057 Jan 83

Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Whereas Plasmodium vivax and Plasmodium knowlesi use the Duffy blood group antigen, Plasmodium falciparum uses sialic acid residues of glycophorin A as receptors to invade human erythrocytes. P. knowlesi uses the Duffy antigen as well as other receptors to invade rhesus erythrocytes by multiple pathways. Parasite ligands that bind these receptors belong to a family of erythrocyte-binding proteins (EBP). The EBP family includes the P. vivax and P. knowlesi Duffy-binding proteins, P. knowlesi beta and gamma proteins, which bind alternate receptors on rhesus erythrocytes, and P. falciparum erythrocyte-binding antigen (EBA-175), which binds sialic acid residues of human glycophorin A. Binding domains of each EBP lie in a conserved N-terminal cysteine-rich region, region II, which contains around 330 amino acids with 12 to 14 conserved cysteines. Regions containing binding residues have now been mapped within P. vivax and P. knowlesi beta region II. Chimeric domains containing P. vivax region II sequences fused to P. knowlesi beta region II sequences were expressed on the surface of COS cells and tested for binding to erythrocytes. Binding residues of P. vivax region II lie in a 170-aa stretch between cysteines 4 and 7, and binding residues of P. knowlesi beta region II lie in a 53-aa stretch between cysteines 4 and 5. Mapping regions responsible for receptor recognition is an important step toward understanding the structural basis for the interaction of these parasite ligands with host receptors.
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PMID:Mapping regions containing binding residues within functional domains of Plasmodium vivax and Plasmodium knowlesi erythrocyte-binding proteins. 1057 Jan 99

Duffy antigen/receptor for chemokines (DARC) is a promiscuous receptor for chemokines that is required for Plasmodium vivax infection of erythroid cells. This receptor is expressed by subsets of endothelial, as well as erythroid cells. Selection for protection from malaria infection resulted in an erythroid-specific defect, suggesting that DARC may play a critical role in endothelial biology. Mice with targeted disruption of this gene were generated, and the function of DARC in inflammation was explored. RNA from spleens of homozygous mutant mice lacked DARC transcripts, which were abundant in wild-type (+/+) and heterozygote (+/-) mice. DARC(-/-) mice lacked developmental abnormalities and were healthy at 1 year. Whereas hematologic parameters were within normal ranges, erythrocytes from nullizygous mice lacked CXC and CC chemokine-binding activity. Challenge with lipopolysaccharide resulted in significantly increased inflammatory infiltrates in lung and liver of nullizygous mice. These results suggest that DARC modulates the intensity of inflammatory reactions as a sink for chemokines. (Blood. 2000;96:1681-1684)
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PMID:Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). 1096 63

Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Plasmodium vivax is completely dependent on interaction with the Duffy blood group antigen to invade human erythrocytes. The P. vivax Duffy-binding protein, which binds the Duffy antigen during invasion, belongs to a family of erythrocyte-binding proteins that also includes Plasmodium falciparum sialic acid binding protein and Plasmodium knowlesi Duffy binding protein. The receptor binding domains of these proteins lie in a conserved, N-terminal, cysteine-rich region, region II, found in each of these proteins. Here, we have expressed P. vivax region II (PvRII), the P. vivax Duffy binding domain, in Escherichia coli. Recombinant PvRII is incorrectly folded and accumulates in inclusion bodies. We have developed methods to refold and purify recombinant PvRII in its functional conformation. Biochemical, biophysical, and functional characterization confirms that recombinant PvRII is pure, homogeneous, and functionally active in that it binds Duffy-positive human erythrocytes with specificity. Refolded PvRII is highly immunogenic and elicits high titer antibodies that can inhibit binding of P. vivax Duffy-binding protein to erythrocytes, providing support for its development as a vaccine candidate for P. vivax malaria. Development of methods to produce functionally active recombinant PvRII is an important step for structural studies as well as vaccine development.
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PMID:Biochemical, biophysical, and functional characterization of bacterially expressed and refolded receptor binding domain of Plasmodium vivax duffy-binding protein. 1127 11

The Duffy blood group antigen is an essential receptor for Plasmodium vivax entry into erythrocytes in a process mediated by the parasite ligand, the Duffy binding protein (DBP). Recently, individuals living in a malaria endemic region of Papua New Guinea were identified as heterozygous for a new allele conferring Duffy negativity, which results in 50% less Duffy antigen on their erythrocytes. We demonstrate that DBP adherence to erythrocytes is significantly reduced for erythrocytes from heterozygous individuals who carry one Duffy antigen negativity allele. These data provide evidence that emergence of this new allelic form of Duffy negativity is correlated with resistance against vivax malaria.
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PMID:Duffy-null promoter heterozygosity reduces DARC expression and abrogates adhesion of the P. vivax ligand required for blood-stage infection. 1132 57


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