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

The Duffy blood group antigen is a serpentine protein with seven transmembrane domains that is not coupled to G-proteins or other known intracellular effectors. In addition to erythrocytes, it is also expressed in endothelial cells and neurons. In recent years the Duffy antigen has received much attention because of its diverse roles in health and disease. These include its functions as a docking receptor for the invasion of human erythrocytes by the malaria parasite Plasmodium vivax. In addition, the Duffy antigen is a binding protein for multiple inflammatory chemokines. Its expression allows erythrocytes to regulate intravascular levels of chemokines. It has also been shown recently that the Duffy antigen plays an important role in endothelial cells by facilitating chemokine transcytosis and presentation. Given these diverse functions of the Duffy antigen, this short review presents detailed methods that can be used to investigate each of these potential roles of this multifaceted protein.
 ...
PMID:Chapter 9 the duffy antigen receptor for chemokines. 1948 Sep 20

The Duffy antigen is the only receptor for Plasmodium vivax, a hemoparasite of the phylum Apicomplexa and the cause of vivax malaria in humans. Resistance to this parasite in the majority of black African individuals and their descendents is due to a mutation in the gene promoter region, which blocks its transcription on erythrocytes. Regarding bovine babesiosis, it is known that taurine breeds are more susceptible to parasite infection than zebuine breeds. In order to verify whether the same human resistance occurs in bovine, the 5' flanking region of the DARC gene was isolated and characterized in Bos indicus and Bos taurus. Four single nucleotide polymorphisms were identified and genotyped (SNP1: EF_647729.1:g.91C>T; SNP2: EF_647729.1:g.405C>T; SNP3: EF_647729.1: g.433A>G and SNP4: EF_647729.1:g.588A>G), which showed significant frequency differences among 99 bovines of each species (n=198). Characterization of the isolated region revealed the presence of 6 putative haplotypes, 14 genotypes, which are formed by haplotypes, and numerous putative transcription factor binding sites. Only the thymine presence on SNPs 1 and 2, more common in B. indicus, was observed to alter some of the sites in this region. Despite this fact, analyses through real-time PCR on bovines that present the most common homozygote genotypes of each species, which contrast for all the polymorphism, revealed no difference on the DARC gene transcription. Thus, in principle, it was concluded that the polymorphisms identified would not be useful as molecular markers in an improvement program for resistance to babesiosis.
 ...
PMID:Characterization and transcriptional analysis of the promoter region of the Duffy blood group, chemokine receptor (DARC) gene in cattle. 1955 88

Plasmodium vivax is the second leading cause of malaria worldwide. Invasion of human erythrocytes by P. vivax merozoites is dependent upon the interaction between the parasite Duffy binding protein (PvDBP) and the erythrocyte Duffy antigen receptor. Therefore, disruption of this vital interaction is an attractive target for therapeutic intervention. Although Aotus nancymaae is a commonly used primate model for human P. vivax infections, it has not been confirmed that the interaction between Ao. nancymaae erythrocytes and P. vivax is Duffy antigen dependent. Our results indicate that normal Ao. nancymaae erythrocytes readily bind to PvDBPII and that this binding is completely abolished with chymotrypsin treatment of the erythrocytes. Furthermore, the results of our inhibition assays show a dose-dependent decrease in binding with increasing amounts of anti-PvDBPII polyclonal rabbit sera or anti-Fy6 monoclonal antibody. These data indicate that the interaction between Ao. nancymaae erythrocytes and P. vivax DBPII is Duffy antigen dependent, validating this model system for in vivo studies of anti-PvDBP inhibition.
 ...
PMID:Plasmodium vivax DBP binding to Aotus nancymaae erythrocytes is Duffy antigen dependent. 1979 92

The Duffy antigen receptor for chemokines (DARC or Fy glycoprotein) carries antigens that are important in blood transfusion and is the main receptor used by Plasmodium vivax to invade reticulocytes. Southeast Asian ovalocytosis (SAO) results from an alteration in RBC membrane protein band 3 and is thought to mitigate susceptibility to falciparum malaria. Expression of some RBC antigens is suppressed by SAO, and we hypothesized that SAO may also reduce Fy expression, potentiallyleading to reduced susceptibility to vivax malaria. Blood samples were collected from individuals living in the Madang Province of Papua New Guinea. Samples were assayed using a flow cytometry assay for expression of Fy on the surface of RBC and reticulocytes by measuring the attachment of a phycoerythrin-labeled Fy6 antibody. Reticulocytes were detected using thiazole orange. The presence of the SAO mutation was confirmed by PCR. There was a small (approximately 10%) but statistically significant (p=0.049, Mann-Whitney U test) increase in Fy expression on SAO RBC compared with RBC from individuals without this polymorphism: mean Fy expression (mean fluorescence intensity [MFI]) was 10.12 +/- 1.22 for SAO heterozygotes versus an MFI of 8.95 +/- 1.1 for individuals without SAO. For reticulocytes the MFI values were 27.61 +/- 19.12 for SAO heterozygotes and 16.47 +/- 3.81 for controls. SAO is associated with increased and not decreased Fy6 expression so that susceptibility to P. vivax infection is unlikely to be affected.
 ...
PMID:Southeast Asian ovalocytosis is associated with increased expression of Duffy antigen receptor for chemokines (DARC). 1992 22

Malaria therapy, experimental, and epidemiological studies have shown that erythrocyte Duffy blood group-negative people, largely of African ancestry, are resistant to erythrocyte Plasmodium vivax infection. These findings established a paradigm that the Duffy antigen is required for P. vivax erythrocyte invasion. P. vivax is endemic in Madagascar, where admixture of Duffy-negative and Duffy-positive populations of diverse ethnic backgrounds has occurred over 2 millennia. There, we investigated susceptibility to P. vivax blood-stage infection and disease in association with Duffy blood group polymorphism. Duffy blood group genotyping identified 72% Duffy-negative individuals (FY*B(ES)/*B(ES)) in community surveys conducted at eight sentinel sites. Flow cytometry and adsorption-elution results confirmed the absence of Duffy antigen expression on Duffy-negative erythrocytes. P. vivax PCR positivity was observed in 8.8% (42/476) of asymptomatic Duffy-negative people. Clinical vivax malaria was identified in Duffy-negative subjects with nine P. vivax monoinfections and eight mixed Plasmodium species infections that included P. vivax (4.9 and 4.4% of 183 participants, respectively). Microscopy examination of blood smears confirmed blood-stage development of P. vivax, including gametocytes. Genotyping of polymorphic surface and microsatellite markers suggested that multiple P. vivax strains were infecting Duffy-negative people. In Madagascar, P. vivax has broken through its dependence on the Duffy antigen for establishing human blood-stage infection and disease. Further studies are necessary to identify the parasite and host molecules that enable this Duffy-independent P. vivax invasion of human erythrocytes.
 ...
PMID:Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. 2023 34

Plasmodium vivax accounts for 65% of all cases of malaria in Asia and South America. Although not usually deadly, this form of malaria continues to inflict misery on the millions of sufferers who have been infected. The paucity of treatments for malaria, coupled with the emerging resistance of the parasite to anti-malarial drugs such as chloroquine, demonstrates an urgent need to develop new and alternative approaches to combat this disease. In this perspective, we propose that the development of small molecule inhibitors of the Duffy antigen, the portal of infection of P. vivax, would be a novel and potentially effective approach for treating this form of malaria.
 ...
PMID:Duffy antigen inhibitors: useful therapeutics for malaria? 2038 62

The Duffy blood group antigen is the portal of entry of the Plasmodiumvivax malaria parasite into human red blood cells and the receptor for a number of CXC and CC chemokines. We review here epidemiological data and evidence derived from therapeutic or experimental human infections associating P. vivax and the Duffy glycoprotein and laboratory studies indicating that P. vivax uses the Duffy antigen as a receptor to invade the red cell. We then review recent field observations indicating that the conclusion of the absolute dependence on the presence of Duffy on the red cell for P. vivax infection and development into the red cell no longer holds true and that in some parts of the world, P. vivax infects and causes disease in Duffy-negative people.
 ...
PMID:Plasmodium vivax and the Duffy antigen: a paradigm revisited. 2065 90

The DARC (Duffy antigen/receptor for chemokines) gene, also called Duffy or FY, encodes a membrane-bound chemokine receptor. Two malaria parasites, Plasmodium vivax and Plasmodium knowlesi, use DARC to trigger internalization into red blood cells. Although much has been reported on the evolution of DARC null alleles, little is known about the evolution of the coding portion of this gene or the role that protein sequence divergence in this receptor may play in disease susceptibility or zoonosis. Here, we show that the Plasmodium interaction domain of DARC is nearly invariant in the human population, suggesting that coding polymorphism there is unlikely to play a role in differential susceptibility to infection. However, an analysis of DARC orthologs from 35 simian primate species reveals high levels of sequence divergence in the Plasmodium interaction domain. Signatures of positive selection in this domain indicate that species-specific mutations in the protein sequence of DARC could serve as barriers to the transmission of Plasmodium between primate species.
 ...
PMID:Species-specific features of DARC, the primate receptor for Plasmodium vivax and Plasmodium knowlesi. 2187 84

We constructed gene knockout mice lacking either the Duffy antigen (Dfy) or glycophorin A (GPA), major glycoproteins that are expressed on erythrocyte membranes, to examine the role of these proteins in malaria infection and erythrocyte. All of the rodent malarias examined proliferated in the erythrocytes of these knockout mice, indicating that neither the Duffy antigen nor GPA has an essential role as a receptor for malaria parasites. Duffy antigen knockout mice infected by Plasmodium yoelii 17XL exhibited autotherapy. At the early stage of the infection, the parasite proliferated exponentially, whereas at the late stage, parasitemia decreased to a level at which the mice were considered cured. The results of depletion experiments with anti-CD4 antibodies suggested that CD4-positive cells in the Duffy antigen knockout mice were responsible for the autotherapy effect. The Duffy antigen is a chemokine receptor. Compared to wild-type mice, chemokines which have affinities for the Duffy antigen injected intravenously more rapidly disappeared from the Duffy antigen knockout mice. Stimulation of the immune response by the increase of leukocytes might lead to the suppression of parasitemia in the Duffy antigen knockout mice. The absence of GPA decreased the amount of O-linked oligosaccharides on the erythrocyte membranes. The erythrocyte membranes of the GPA knockout mice decreased several O-linked glycoproteins and TER-119 protein. GPA has an essential role in the expression of O-linked antigens on erythrocyte membranes, but these proteins are not important for malaria parasite invasion of erythrocytes.
 ...
PMID:Roles of the Duffy antigen and glycophorin A in malaria infectionand erythrocyte. 2250

Resistance to Plasmodium vivax blood-stage infection has been widely recognised to result from absence of the Duffy (Fy) blood group from the surface of red blood cells (RBCs) in individuals of African descent. Interestingly, recent studies from different malaria-endemic regions have begun to reveal new perspectives on the association between Duffy gene polymorphism and P. vivax malaria. In Papua New Guinea and the Americas, heterozygous carriers of a Duffy-negative allele are less susceptible to P. vivax infection than Duffy-positive homozygotes. In Brazil, studies show that the Fy(a) antigen, compared to Fy(b), is associated with lower binding to the P. vivax Duffy-binding protein and reduced susceptibility to vivax malaria. Additionally, it is interesting that numerous studies have now shown that P. vivax can infect RBCs and cause clinical disease in Duffy-negative people. This suggests that the relationship between P. vivax and the Duffy antigen is more complex than customarily described. Evidence of P. vivax Duffy-independent red cell invasion indicates that the parasite must be evolving alternative red cell invasion pathways. In this chapter, we review the evidence for P. vivax Duffy-dependent and Duffy-independent red cell invasion. We also consider the influence of further host gene polymorphism associated with malaria endemicity on susceptibility to vivax malaria. The interaction between the parasite and the RBC has significant potential to influence the effectiveness of P. vivax-specific vaccines and drug treatments. Ultimately, the relationships between red cell polymorphisms and P. vivax blood-stage infection will influence our estimates on the population at risk and efforts to eliminate vivax malaria.
 ...
PMID:Red blood cell polymorphism and susceptibility to Plasmodium vivax. 2338 21


<< Previous 1 2 3 4 5 6 7 Next >>