Hemopoietic Cell Expression of the Chemokine Decoy Receptor D6 Is Dynamic and Regulated by GATA1

McKimmie, Clive S.; Fraser, Alasdair R.; Hansell, Chris; Gutiérrez, Laura; Philipsen, Sjaak; Connell, Laura; Rot, Antal; Kurowska‐Stolarska, Mariola; Carreño, Paz; Pruenster, Monika; Chu, Chung-Ching; Lombardi, Giovanna; Halsey, Christina; McInnes, Iain B.; Liew, Foo Y.; Nibbs, Robert J. B.; Graham, Gerard J.

doi:10.4049/jimmunol.181.5.3353

Cited by 69 publications

(40 citation statements)

References 51 publications

(54 reference statements)

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“…Although CCL2 can also bind to D6 and Duffy/DARC “decoy” receptors [29], the expression of these receptors in monocytes is low or undetectable [14, 15]. This is consistent with previous studies which identify a single class of high affinity receptor for CCL2 in human monocytes [23, 26].…”

Section: Discussionsupporting

confidence: 84%

Porcine monocyte subsets differ in the expression of CCR2 and in their responsiveness to CCL2

Moreno¹,

Álvarez²,

Poderoso³

et al. 2010

Vet. Res.

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Monocyte subsets have been shown to differ in the pattern of chemokine receptor expression and their migratory properties, both in human and mouse. Previously we have characterized in the swine several monocyte subpopulations, based on the expression of CD163, Tük4 and SLA-II, which share features with the populations described in human and mouse. Here, we have analysed the expression of different chemokine receptors in the CD163−Tük4+SLA-II− and CD163+Tük4−SLA-II+ populations of porcine monocytes. CD163+Tük4−SLA-II+ monocytes expressed higher CX3CR1 but lower CCR2 and CXCR4 mRNA levels than CD163−Tük4+SLA-II− monocytes. Moreover, porcine CCL2 binding on Tük4+SLA-II− but not on Tük4−SLA-II+ cells was detected by using a CCL2-green fluorescence protein (pCCL2-GFP) fusion protein. Finally, flow cytometric analyses of monocytes recovered after chemotaxis assays show a clear increase in the proportion of Tük4+SLA-II− cells in the fraction migrating toward CCL2, consistent with the polarized CCR2 expression in this monocyte population. The pattern of expression of these chemokine receptors reinforces the similarities of these porcine subsets with their human and mouse counterparts.

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Section: Discussionsupporting

confidence: 84%

Porcine monocyte subsets differ in the expression of CCR2 and in their responsiveness to CCL2

Moreno¹,

Álvarez²,

Poderoso³

et al. 2010

Vet. Res.

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show abstract

“…In adult tissues, ACKR2 is expressed on some but not all lymphatic endothelial cells, in both peripheral tissues and lymphoid organs (Nibbs et al, 2001;Lee et al, 2011). In addition, ACKR2 is expressed by a range of leukocyte subtypes, most notably dendritic cells and innate-like B cells (McKimmie et al, 2008;Hansell et al, 2011).…”

Section: B Ackr2 (Formerly D6 or Ccbp2)mentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

et al. 2013

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“…1H). Real-time PCR was performed as described previously (24,25), and samples were tested in triplicate using cDNA (1 g total RNA transcribed), 2ϫ Per-feCTa SYBR green fast mix (Quanta Bioscience), 500 M forward and reverse primer mix, and RNase-free water according to the manufacturer's protocol. All primers used for quantitative RT-PCR (qRT-PCR) were designed using Primer 3 software and manufactured by IDT technologies.…”

Section: Mice and Virus Infectionmentioning

confidence: 99%

Defining the Chemokine Basis for Leukocyte Recruitment during Viral Encephalitis

Michlmayr

McKimmie

Pingen

et al. 2014

J Virol

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The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. IMPORTANCEBrain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of encephalitis is the recruitment of inflammatory leukocytes to the infected brain, a process driven by members of the chemokine family. Here we provide an in-depth analysis of the chemokines involved in leukocyte recruitment to the virally infected brain and demonstrate that simultaneous blockade of two of these receptors, namely, CXCR3 and CCR2, does not alter viral titers within the brain but markedly reduces inflammatory leukocyte recruitment and enhances survival in a murine model of lethal viral encephalitis. Our results therefore highlight chemokine receptors as plausible therapeutic targets in treating viral encephalitis.

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Hemopoietic Cell Expression of the Chemokine Decoy Receptor D6 Is Dynamic and Regulated by GATA1

Cited by 69 publications

References 51 publications

Porcine monocyte subsets differ in the expression of CCR2 and in their responsiveness to CCL2

Porcine monocyte subsets differ in the expression of CCR2 and in their responsiveness to CCL2

International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

Defining the Chemokine Basis for Leukocyte Recruitment during Viral Encephalitis

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