Shedding light on DARC: the role of the Duffy antigen/receptor for chemokines in inflammation, infection and malignancy

Horne, Kylie; Woolley, Ian

doi:10.1007/s00011-009-0023-9

Cited by 33 publications

(28 citation statements)

References 37 publications

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“…It has been involved in allogeneic rejection of lung and renal transplants (70,71). This CD8-binding and sialic acid-containing glycoprotein has been associated with neutrophil activation through NAP-2 and NAP-3-dependent mechanisms (72). It is therefore tempting to speculate that CD82-Duffy Ag/receptor for chemokine interactions may also occur during the xenogeneic encounter.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Tetraspanin CD82 as a New Barrier to Xenotransplantation

Saleh

Parhar

Al-Hejailan

et al. 2013

The Journal of Immunology

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Significant immunological obstacles are to be negotiated before xenotransplantation becomes a clinical reality. An initial rejection of transplanted vascularized xenograft is attributed to Galα1,3Galβ1,4GlcNAc-R (Galα1,3-Gal)–dependent and –independent mechanisms. Hitherto, no receptor molecule has been identified that could account for Galα1,3-Gal–independent rejection. In this study, we identify the tetraspanin CD82 as a receptor molecule for the Galα1,3-Gal–independent mechanism. We demonstrate that, in contrast to human undifferentiated myeloid cell lines, differentiated cell lines are capable of recognizing xenogeneic porcine aortic endothelial cells in a calcium-dependent manner. Transcriptome-wide analysis to identify the differentially expressed transcripts in these cells revealed that the most likely candidate of the Galα1,3-Gal–independent recognition moiety is the tetraspanin CD82. Abs to CD82 inhibited the calcium response and the subsequent activation invoked by xenogeneic encounter. Our data identify CD82 on innate immune cells as a major “xenogenicity sensor” and open new avenues of intervention to making xenotransplantation a clinical reality.

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Section: Discussionmentioning

confidence: 99%

Identification of the Tetraspanin CD82 as a New Barrier to Xenotransplantation

Saleh

Parhar

Al-Hejailan

et al. 2013

The Journal of Immunology

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“…Others studies have shown that mice lacking the CCR5 receptor present a significant reduction of cardiac inflammatory infiltrate, suggesting the importance of this receptor in lymphocyte migration and control of local parasite replication (82). It is important to emphasize that DARC presents a significant homology with receptor CCR5, and it is also a receptor for chemokine CCL5 (55).…”

Section: Darc and Chagas' Diseasementioning

confidence: 98%

“…However, the theory that DARC plays a "sink" function has been questioned. Some authors have demonstrated that there is no chemokine intracellular variation associated to DARC (55). Thus, further investigations are needed to better understand this role of DARC.…”

Section: Introductionmentioning

confidence: 99%

“…Susceptibility to asthma was correlated with the absence of DARC expression in red cells from certain Afro-descendant populations (61). A recent study showed that the absence of DARC in erythrocytes resulted in a 40% increase in the risk of acquiring HIV; however, these individuals presented a short-term progression of the disease (55,62). Epidemiological data suggest that DARC absence in the erythrocyte has contributed to an increase in prostate cancer incidence and mortality (46,63).…”

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confidence: 99%

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Chagas' disease and Duffy antigen/receptor for chemokine (DARC): a mini-review

Oliveira¹,

Mattos²,

Cavasini³

2011

J. Venom. Anim. Toxins incl. Trop. Dis

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Duffy gene (FY) codifies the transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system which were designated receptors for chemokines and denominated DARC (Duffy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing inflammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an inflammatory disease, in which infiltrated inflammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profile of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this inflammatory disease.Key words: DARC antigen, Duffy blood-group system, Chagas' disease, Chagas' cardiomyopathy. Review ARticle INTRODUCTIONThe Duffy gene (FY) codifies the moderately immunogenic transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa (1). This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system, which are codified by FYA and FYB alleles of the FY gene playing a codominant role. The FYA and FYB alleles differ due to substitution of the base G by another A in the 125 nucleotide, which develops a common polymorphism in the Caucasian population. This single nucleotide polymorphism (SNP) results in the substitution of amino acid glycine by asparagine in position 42 (2).Although this polymorphism originates distinct glycoproteins called Fya and Fyb antigens, both have moderate immunogenicity.They can be identified with the use of antiFya and anti-Fyb anti-sera, allowing the characterization of four erythrocyte phenotypes: Fy(a+b-), Fy(a-b+), Fy(a+b+) and Fy(a-b-) (3, 4). Negative phenotype Duffy [Fy(a-b-)] is the result of a variant FYB allele (FYB-33), which presents a single point mutation where there is a T to C substitution in nucleotide -33 (-33T>C), also known as the GATA-BOX, located in the promoter region of the FY gene (5, 6).The differential distribution of DARC antigenic determinant between ethnic groups is a characteristic of this histo-blood system. As an example, FYA is prevalent in European, Chinese, Japanese, and Malaysian populations, but rarely in African population. And on the other hand, in Caucasians, FYB is widely found compared to Asian and African populations (7, 8 (25)(26)(27)(28). Genetic mechanisms for the Duffy-negative phenotype in erythrocytes have preserved its expression in the endothelium determining an important role in inflammation physiopathology (16, 19).Antigens...

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“…This condition is now known to arise as a result of a -46 T to C substitution in the Duffy Antigen Receptor for Chemokines (DARC) gene. This variant has been associated with altered recruitment of leukocytes to sites of inflammation (76), and the gene on red blood cells is capable of binding chemokines and may diminish WBC numbers in part by modulating chemokine signaling in the bone marrow (as it can sequester molecules through membrane binding). Numerous subtle immune alterations have been associated with this variant, including modulation of chemokine concentrations in vascular and tissue microenvironments (77), and alterations in endotoxin reactivity (78).…”

Section: Characteristics and Environmental Factors Impacting Immunolomentioning

confidence: 99%

Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research

Michaud

Houseman

Marsit

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Understanding the precise role of the immune system in cancer has been hindered by the complexity of the immune response and challenges in measuring immune cell types in health and disease in the context of large epidemiologic studies. In this review, we present the rationale to study immunity in cancer and highlight newly available tools to further elucidate the epidemiologic factors driving individual variation in the immune response in cancer. Here, we summarize key studies that have evaluated the role of immunologic status on risk of cancer, discuss tools that have been used in epidemiologic studies to measure immune status, as well as new evolving methodologies where application to epidemiology is becoming more feasible. We also encourage further development of novel emerging technologies that will continue to enable prospective assessment of the dynamic and complex role played by the immune system in cancer susceptibility. Finally, we summarize characteristics and environmental factors that affect the immune response, as these will need to be considered in epidemiologic settings. Overall, we consider the application of a systems biologic approach and highlight new opportunities to understand the immune response in cancer risk.

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Shedding light on DARC: the role of the Duffy antigen/receptor for chemokines in inflammation, infection and malignancy

Cited by 33 publications

References 37 publications

Identification of the Tetraspanin CD82 as a New Barrier to Xenotransplantation

Identification of the Tetraspanin CD82 as a New Barrier to Xenotransplantation

Chagas' disease and Duffy antigen/receptor for chemokine (DARC): a mini-review

Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research

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