Molecular mechanisms that lead to reduced expression of Duffy antigens

Yazdanbakhsh, Karina; Rios, María; Storry, Jill R.; Kosower, Nechama S.; Parasol, Niva; Chaudhuri, Asok; Reid, Marion E.

doi:10.1046/j.1537-2995.2000.40030310.x

Cited by 77 publications

(87 citation statements)

References 44 publications

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“…The determination of the Gly42Asp (G125A), Arg89Cys (C265T), Ala100Thr (G298A) polymorphisms of the Duffy gene (FY) coding region followed the protocol suggested by Parasol et al (1998), and the T33C polymorphism determination of the Duffy gene (FY) promoter region (GATA-1 box) followed the protocol suggested by Yazdanbakhsh et al (2000). For the above polymorphisms the following restriction enzymes were used: BstXI, BanI, Acil, MwoI (New England Biolabs, MA, USA) and StyI (Gibco BRL, MD, USA), respectively, and the fragments were analyzed on 8% polyacrylamide gel (Figure 1 and Figure 2A, B, C, respectively).…”

Section: Restriction Fragment Length Polymorphism Determinationmentioning

confidence: 99%

Genetic polymorphisms in TLR4, CR1 and Duffy genes are not associated with malaria resistance in patients from Baixo Amazonas region, Brazil

Soares

Abe‐Sandes²,

Filho³

et al. 2008

Genet. Mol. Res.

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ABSTRACT. The main purpose of this research was to analyze the relation of the genetic polymorphisms frequently expressed by antigen-presenting cells, erythrocytes and malaria susceptibility/resistance with the human malaria infection cases. The sample used consisted of 23 Plasmodium vivax (Pv)-and P. falciparum (Pf)-infected patients, and 21 healthy individuals as a control group, from the Baixo Amazonas population in Pará, Brazil. The Asp299Gly polymorphisms in the Toll-like receptor 4 (TLR4), and Gly42Asp, Arg89Cys, Ala100Thr, and T-33C in the Duffy gene (FY) were analyzed by restriction fragment length polymorphism-polymerase chain reaction. The Lys1590Glu and Arg1601Gly polymorphisms in the complement receptor type 1 (CR1) were analyzed by DNA sequencing. According to the results obtained and statistical analysis considering a significance level or α = 0.01, we conclude that the low heterozygote frequency (2.27%) for the Asp299Gly mutation, detected in the TLR4 gene, is not related to the Pv and Pf infections in the patients analyzed. Also, the promoter region GATA-1 analysis of the FY gene in the Pv-infected patients showed that the heterozygote frequency for the T-33C mutation (11.36% of the infected patients and 20.45% of the control patients) is not related to infection resistance. Regarding the CR1 gene, the observed heterozygote frequency (9.09%) for the Arg1601Gly mutation in Pf-infected patients when compared to heterozygote frequency in the control group (18.18%) suggests that there is no correlation with infection resistance.

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Section: Restriction Fragment Length Polymorphism Determinationmentioning

confidence: 99%

Genetic polymorphisms in TLR4, CR1 and Duffy genes are not associated with malaria resistance in patients from Baixo Amazonas region, Brazil

Soares

Abe‐Sandes²,

Filho³

et al. 2008

Genet. Mol. Res.

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“…Because of the codominant expression of the Duffy Ag alleles, individuals heterozygous (AG) for the GATA-1 box polymorphism have previously been shown to have only 50% of the expected amount of erythrocyte chemokine binding, as compared with individuals without the GATA-1 box polymorphism (15). Table I summarizes plasma cytokine concentrations obtained after stimulation of whole blood with LPS in vitro.…”

Section: Influence Of the Duffy Ag On Chemokine Concentrations In Thementioning

confidence: 99%

“…Approximately 68% of African Americans and Ͼ95% of West Africans lack Duffy Ag on their RBC (10,14) and, therefore, do not demonstrate chemokine binding on erythrocytes (10,15). However, Duffy Ag expression has been subsequently identified along splenic sinusoids and postcapillary venules using tissue from individuals lacking erythrocyte Duffy Ag (16).…”

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confidence: 99%

“…To test this hypothesis, we first determined whether Duffy Ag "loss-offunction" phenotypes (human and murine) are associated with alterations in plasma chemokine concentrations following an inflammatory stimulus of whole blood in vitro. We studied the GATA-1 box polymorphism of the human Duffy Ag gene that abrogates erythrocyte Duffy expression (17) and erythrocyte chemokine binding (2,15). We also studied the FyX mutation arising from the Arg 89 Cys substitution, which results in significantly less membrane expression of the Duffy Ag, and ϳ75% less chemokine binding by erythrocytes from homozygous individuals (15).…”

mentioning

confidence: 99%

“…We studied the GATA-1 box polymorphism of the human Duffy Ag gene that abrogates erythrocyte Duffy expression (17) and erythrocyte chemokine binding (2,15). We also studied the FyX mutation arising from the Arg 89 Cys substitution, which results in significantly less membrane expression of the Duffy Ag, and ϳ75% less chemokine binding by erythrocytes from homozygous individuals (15). We then determined the in vivo contribution of erythrocyte and endothelial Duffy Ag in modifying neutrophil recruitment and chemokine concentrations in the airspace, lung tissue vascular space, and plasma compartments following an inflammatory stimulus arising from the lungs.…”

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confidence: 99%

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The Duffy Antigen Modifies Systemic and Local Tissue Chemokine Responses following Lipopolysaccharide Stimulation

Lee

Wurfel

Matute-Bello

et al. 2006

The Journal of Immunology

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The Duffy blood group Ag (dfy) binds selective CXC and CC chemokines at high affinity and is expressed on erythrocytes and endothelial cells. However, it does not transmit a signal via G proteins, as occurs with other seven-transmembrane receptors. We hypothesized that dfy functions as a chemokine reservoir and regulates inflammation by altering soluble chemokine concentrations in the blood and tissue compartments. We determined whether Duffy Ag “loss-of-function” phenotypes (human and murine) are associated with alterations in plasma chemokine concentrations during the innate inflammatory response to LPS. Plasma CXCL8 and CCL2 concentrations from humans homozygous for the GATA-1 box polymorphism, a dfy polymorphism that abrogates erythrocyte chemokine binding, were higher than in heterozygotes following LPS stimulation of their whole blood in vitro. Similarly, dfy−/− mice showed higher plasma MIP-2 concentrations than dfy+/+ mice following LPS stimulation of whole blood in vitro. We then determined the relative contributions of erythrocyte and endothelial Duffy Ag in modifying chemokine concentrations and neutrophil recruitment in the lungs following intratracheal LPS administration in dfy−/− and dfy+/+ mice reconstituted with dfy−/− or dfy+/+ marrow. Mice lacking endothelial dfy expression had higher MIP-2 and keratinocyte chemoattractant concentrations in the airspaces. Mice lacking erythrocyte dfy had higher MIP-2 and keratinocyte chemoattractant concentrations in the lung tissue vascular space, but lower plasma chemokine concentrations associated with attenuated neutrophil recruitment into the airspaces. These data indicate that dfy alters soluble chemokine concentrations in blood and local tissue compartments and enhances systemic bioavailability of chemokines produced during local tissue inflammation.

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Duffy Blood Group System

2002

Human Blood Groups

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Molecular mechanisms that lead to reduced expression of Duffy antigens

Abstract: Reduced Duffy expression can result from mutations affecting transcription (mutated GATA box in one allele) or instability of the translated protein (Arg89Cys). The frequencies of these mutations vary among populations.

Cited by 77 publications

References 44 publications

Genetic polymorphisms in TLR4, CR1 and Duffy genes are not associated with malaria resistance in patients from Baixo Amazonas region, Brazil

Genetic polymorphisms in TLR4, CR1 and Duffy genes are not associated with malaria resistance in patients from Baixo Amazonas region, Brazil

The Duffy Antigen Modifies Systemic and Local Tissue Chemokine Responses following Lipopolysaccharide Stimulation

Duffy Blood Group System

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