The human Duffy antigen binds selected inflammatory but not homeostatic chemokines

Gardner, Lucy; Patterson, Angela; Ashton, Brian A.; Stone, Michael A.; Middleton, Jim

doi:10.1016/j.bbrc.2004.06.146

Cited by 108 publications

(107 citation statements)

References 42 publications

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“…DARC is a seven transmembrane protein that binds a variety of pro-inflammatory CC and CXC chemokines [18,19]. It was first identified as a red blood group antigen involved in transfusion reactions and was later shown to be a co-receptor for malaria parasites [13,[20][21][22].…”

Section: Discussionmentioning

confidence: 99%

The role of chemokine receptors in acute lung allograft rejection

Geleff

Draganovici²,

Jaksch³

et al. 2009

Eur Respir J

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Recruitment of inflammatory cells to vascularised allografts is a hallmark of rejection, and paves the way for chronic allograft injury. Chemokines play pivotal roles in the directed movement of leukocytes. Herein, we define the distribution of chemokine receptors for the most common cell types during human lung allograft rejection as a prerequisite for therapeutic interventions.Immunohistochemistry was performed on lung allograft biopsies from 54 patients for the chemokine receptors CCR5, CXCR3 and CXCR1 and the Duffy antigen/receptor for chemokines (DARC).Perivascular infiltrates in acute lung rejection are composed of subsets of mononuclear cells expressing the chemokine receptors CXCR1, CXCR3 and CCR5. DARC-positive small vessels and capillary vessels were associated with sites of inflammation and their number was increased during episodes of acute lung rejection. DARC expression correlated with an increase in interstitial CCR5-positive T-cells and CXCR1-positive leukocytes. Leucokytic infiltrates in bronchial/bronchiolar rejection express CXCR1 and CXCR3. This is the first study that demonstrates an induction of the chemokine binding protein DARC at sites of acute human lung allograft rejection. Co-localisation with the chemokine receptors CXCR1 and CCR5 may indicate a role for DARC expression during leukocyte adhesion and interstitial infiltration.

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Section: Discussionmentioning

confidence: 99%

The role of chemokine receptors in acute lung allograft rejection

Geleff

Draganovici²,

Jaksch³

et al. 2009

Eur Respir J

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“…It binds several proinflammatory chemokines of both the CXC and CC subfamilies but does not bind homeostatic chemokines. 84 Recent evidence suggests Duffy protein on endothelial cells binds chemokines and facilitates leukocyte extravasation contributing to disease pathogenesis through inflammation. 85 Evidence for up-regulation of Duffy expression in the vascular endothelium during infection and transplant rejection supports this view.…”

Section: Plasmodium Vivax and The Blood Group Fy(a؊b؊) Phenotypementioning

confidence: 99%

The relationship between blood groups and disease

Anstee

2010

Blood

384

349

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The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. IntroductionHirszfeld and Hirszfeld 1 showed the frequencies of blood groups A and B differ between populations. Their observations raised fundamental questions regarding the causes of these differences, which were eloquently summarized by Mourant et al 2(p1) :Were the differences the result of random genetic drift and founder effects, in small populations which later multiplied and stabilized the original, fortuitous, frequencies, or were they the result of natural selection, arising from differences in fitness between the various blood groups, fitnesses which themselves depended upon locally determined features of the external environment?Mourant et al concluded that "most workers now agree that both processes are operative, but their relative importance remains in question." 2 We now have detailed information concerning almost all the genes giving rise to blood group polymorphisms, the structure of the gene products and the antigens themselves, and in many cases functional information sufficient to delineate mechanisms of interaction with external agents. [3][4][5] In addition, studies on the tracking of Y chromosome and mtDNA haplotypes in human populations provide us with unprecedented information concerning the significance of genetic drift and founder effects in determining the genetic background of different world populations. 6 Given this new information, it seems an appropriate time to revisit these questions and ask whether we are any nearer understanding the relative importance of natural selection and founder effects in determining the distribution of human blood groups. Infectious diseases and selection for ABO blood group antigensThe molecular basis of the ABO blood group system was elucidated in 1990. 7 The gene encodes a glycosyltransferase, which transfers N-acetyl D-galactosamine (group A) or D-galactose (group B) to the nonreducing ends of glycans on glycoproteins and glycolipids. The group O phenotype results from inactivation of the A1 glycosyltransferase gene, and the nonreducing ends of the corresponding glycans in group O subjects express the blood group H antigen ( Figure 1A). The ABH antigens are not confined to red cells but are widely expressed i...

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“…In the early 1990s it was recognised that this molecule was a seven transmembrane spanning receptor and later that it bound, with high affinity, inflammatory CC and CXC chemokines [24][25][26][27][28]. It is, thus far, the only mammalian chemokine receptor capable of binding ligands from more than one chemokine subfamily (Table 1).…”

Section: The Darcmentioning

confidence: 99%

D6 and the atypical chemokine receptor family: Novel regulators of immune and inflammatory processes

2009

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Chemokines are key regulators of leukocyte migration and play important roles in a number of physiological and pathological immune and inflammatory contexts. In addition to the classical signalling chemokine receptors there has emerged, recently, a new subclass of atypical chemokine receptors. This subfamily is characterised by an apparent lack of signalling and, in some cases, by an ability to internalise and degrade chemokine ligands. This review describes the family of atypical chemokine receptors with particular emphasis on the D6 receptor. The in vitro and in vivo biology of D6 is described, which indicates that D6 is active as a scavenger of inflammatory CC-chemokines and appears to play essential roles in the regulation of inflammatory responses.Key words: Chemokines . Immune regulation . Inflammation IntroductionThe movement of leukocytes during immune and inflammatory responses is a carefully orchestrated process that ensures coordinated cellular migration in response to physiological and pathological cues. Prominent amongst the regulators of leukocyte movement are the members of the chemokine family [1]. Chemokines are small proteins (8-12 kDa) and membership of the chemokine family is defined on the basis of the presence of variations on a conserved cysteine motif in the mature section of the proteins. Chemokines can be assigned to one of four subfamilies according to the specific nature of this motif. The majority of chemokines have four cysteines with 28 chemokines being assigned to the CC family (so-called because of the juxtaposition of the first two cysteine residues) and 16 being assigned to the CXC family (which possess a single variable amino acid between the first two cysteines). The two smaller subfamilies are represented by single members and are the CX3C family (three amino acids between the first two cyteines) and the XC family, which lacks the first and third cyteines seen in the other family members. Much confusion arose in the mid-1990s due to the complex and variable nomenclature used to refer to chemokines. For this reason a systematic nomenclature system has been adopted, which refers to the chemokines as ligands of each of the subfamilies and numbers them according to when their sequences were first deposited in the Genbank databases [2]. Thus, CCL1 is the first CC chemokine to be identified and CCL28 the most recent. Chemokines and their roles in leukocyte migrationFunctionally, chemokines are known to be pleiotropic. However, their main role is in the regulation of leukocyte migration. In this context we can define chemokines as being either homeostatic/ constitutive or inflammatory according to the contexts in which they function [2,3]. Homeostatic chemokinesThe homeostatic chemokines are important for the regulation of basal leukocyte trafficking and regulate processes such as the Mini-Reviewtissue-specific migration of T cells and the homing of DC to draining lymph nodes [4][5][6]. In combination with adhesion molecules, the homeostatic chemokines can form part of a very spec...

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The human Duffy antigen binds selected inflammatory but not homeostatic chemokines

Cited by 108 publications

References 42 publications

The role of chemokine receptors in acute lung allograft rejection

The role of chemokine receptors in acute lung allograft rejection

The relationship between blood groups and disease

D6 and the atypical chemokine receptor family: Novel regulators of immune and inflammatory processes

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