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

Lee, Janet; Wurfel, Mark M.; Matute-Bello, Gustavo; Frevert, Charles W.; Rosengart, Matthew R.; Ranganathan, Mrunalini; Wong, Venus; Holden, Tarah D.; Sutlief, S.; Richmond, Ann; Peiper, Stephen C.; Martin, Thomas R.

doi:10.4049/jimmunol.177.11.8086

Cited by 78 publications

(86 citation statements)

References 37 publications

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“…37 Supporting this, studies in mouse models show that DARC expression on both RBC and endothelial cells influences neutrophil migration. 38,39 In addition, DARC Ϫ46C/C may associate with impaired hematopoiesis because some of the chemokines that bind to DARC (eg, GRO␣ 40 ) regulate many hematopoietic responses, including survival, proliferation, migration, and homing. 41 Supporting this possibility, healthy subjects of African ancestry have reduced numbers of bone marrow progenitor cells than Caucasians.…”

Section: Discussionmentioning

confidence: 99%

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry

Kulkarni

Marconi

et al. 2009

Blood

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Persons of African ancestry, on average, have lower white blood cell (WBC) counts than those of European descent (ethnic leukopenia), but whether this impacts negatively on HIV-1 disease course remains unknown. Here, in a large natural history cohort of HIV-infected subjects, we show that, although leukopenia (< 4000 WBC/mm 3 during infection) was associated with an accelerated HIV disease course, this effect was more prominent in leukopenic subjects of European than African ancestry. The Africanspecific ؊46C/C genotype of Duffy Antigen Receptor for Chemokines (DARC) confers the malaria-resisting, Duffy-null phenotype, and we found that the recently described association of this genotype with ethnic leukopenia extends to HIV-infected African Americans (AAs). The association of Duffy-null status with HIV disease course differed according to WBC but not CD4 ؉ T-cell counts, such that leukopenic but not nonleukopenic HIV ؉ AAs with DARC ؊46C/C had a survival advantage compared with all Duffypositive subjects. This survival advantage became increasingly pronounced in those with progressively lower WBC counts. These data highlight that the interaction between DARC genotype and the cellular milieu defined by WBC counts may influence HIV disease course, and this may provide a partial explanation of why ethnic leukopenia remains benign in HIVinfected AAs, despite immunodeficiency.

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Section: Discussionmentioning

confidence: 99%

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry

Kulkarni

Marconi

et al. 2009

Blood

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“…An exaggerated inflammatory response observed in the lungs and liver of DARC knockout mice is consistent with the idea that the molecule functions as a chemokine-clearing receptor (19). It has been suggested that DARC may limit the actions of chemokines and alter allergic inflammation (20,21).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Gene Encoding Duffy Antigen/Receptor for Chemokines Is Associated with Asthma and IgE in Three Populations

Vergara¹,

Tsai²,

Grant³

et al. 2008

Am J Respir Crit Care Med

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Rationale: Asthma prevalence and severity are high among underserved minorities, including those of African descent. The Duffy antigen/receptor for chemokines is the receptor for Plasmodium vivax on erythrocytes and functions as a chemokine-clearing receptor. Unlike European populations, decreased expression of the receptor on erythrocytes is common among populations of African descent, and results from a functional T-46C polymorphism (rs2814778) in the promoter. This variant provides an evolutionary advantage in malaria-endemic regions, because Duffy antigen/receptor for chemokines-negative erythrocytes are more resistant to infection by P. vivax. Objectives: To determine the role of the rs2814778 polymorphism in asthma and atopy as measured by total serum IgE levels among four populations of African descent (African Caribbean, African American, Brazilian, and Colombian) and a European American population. Methods: Family-based association tests were performed in each of the five populations to test for association between the rs2814778 polymorphism and asthma or total IgE concentration. Measurements and Main Results: Asthma was significantly associated with the rs2814778 polymorphism in the African Caribbean, Colombian, and Brazilian families (P , 0.05). High total IgE levels were associated with this variant in African Caribbean and Colombian families (P , 0.05). The variant allele was not polymorphic among European Americans. Conclusions: Susceptibility to asthma and atopy among certain populations of African descent is influenced by a functional polymorphism in the gene encoding Duffy antigen/receptor for chemokines. This genetic variant, which confers resistance to malarial parasitic infection, may also partially explain ethnic differences in morbidity of asthma.

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“…However, it does not transmit a signal via G proteins, as occurs with other seven-transmembrane receptors. The receptor serves as a chemokine reservoir, regulating tissue and plasma chemokine levels, thus affecting neutrophil migration to various tissues, including the lung [80][81][82][83]. Mice deficient in this receptor demonstrate impaired neutrophil migration to the lung, intestines and peritoneum, and altered chemokine levels in the serum and tissue [82,83].…”

Section: Modification Of Chemokine Gradients In Alimentioning

confidence: 99%

“…The receptor serves as a chemokine reservoir, regulating tissue and plasma chemokine levels, thus affecting neutrophil migration to various tissues, including the lung [80][81][82][83]. Mice deficient in this receptor demonstrate impaired neutrophil migration to the lung, intestines and peritoneum, and altered chemokine levels in the serum and tissue [82,83]. In endothelial cells expressing the Duffy antigen, neutrophil migration toward GRO-α/CXCL1 and IL-8 (IL-8/CXCL8) was enhanced, suggesting that the Duffy antigen participates in the movement of neutrophil chemokines across the endothelium [81].…”

Section: Modification Of Chemokine Gradients In Alimentioning

confidence: 99%

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Manicone¹

2009

Expert Review of Clinical Immunology

113

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Acute lung injury (ALI) is a clinical disease marked by respiratory failure due to disruption of the epithelial and endothelial barrier, flooding of the alveolar compartment with protein-rich fluid and recruitment of neutrophils into the alveolar space. ALI affects approximately 200,000 patients annually in the USA and results in approximately 75,000 deaths. It is associated with prolonged mechanical ventilation, intensive medical care, high morbidity and mortality, and rising healthcare costs. Owing to its impact on public health, great strides have been made towards understanding the pathobiology of ALI to affect outcome. This review will focus on the role of the epithelial cell in the pathogenesis and resolution of ALI and the role of various inflammatory mediators in ALI. Keywordsβ2-agonist; acute lung injury; acute respiratory distress syndrome; chemokine; cytokine; epithelial cell; inflammation; methylprednisolone; neutrophil; salbutamol; steroid; ventilator-induced lung injuryAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) was first described in 1967 by Ashbaugh and colleagues in a group of 12 patients who shared a constellation of clinical symptoms including acute respiratory distress, hypoxemia refractory to supplemental oxygen, decreased lung compliance and diffuse pulmonary infiltrates [1]. Since this first description, the clinical criteria have evolved to include acute onset of respiratory distress, bilateral pulmonary infiltrates seen on chest radiographs, absence of left-sided heart failure and hypoxemia, with the severity of hypoxemia distinguishing ALI and ARDS (Box 1) [2]. Extrapolating from recent epidemiologic studies using these criteria, ALI affects about 200,000 patients annually in the USA and results in approximately 75,000 deaths [3]. This disease, which can be caused by common events such as pneumonia, sepsis and trauma, results in high morbidity, mortality and healthcare expenditures associated with prolonged mechanical ventilation and intensive care. Because of its impact on public health and patient outcomes, great strides have been made towards understanding the pathobiology of ALI.When defined broadly to include all processes related to defense against microbes, other environmental insults and injury, a wide variety of cell types and proteins participate in inflammation and immunity. Leukocytes are the paradigmatic inflammatory cell type, but they are not the only cells that function in defense and immunity. The epithelial lining of all tissues forms a continuous barrier to the environment and is the first line of defense against infectious agents and toxins. Though specialized to serve distinct functions among tissues, epithelial cells respond similarly to injury and infection, and regulate leukocyte influx through the production of proinflammatory cytokines, chemokines and other factors that modulate chemokine gradients and effect leukocyte migration. This review will focus on the role of the pulmonary epithelium and inflammatory mediators in ALI. More s...

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

Cited by 78 publications

References 37 publications

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry

Gene Encoding Duffy Antigen/Receptor for Chemokines Is Associated with Asthma and IgE in Three Populations

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

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