scholarly journals Identification of C-C Chemokine Receptor 1 (CCR1) as the Monocyte Hemofiltrate C-C Chemokine (HCC)-1 Receptor

1998 ◽  
Vol 188 (3) ◽  
pp. 603-608 ◽  
Author(s):  
Chia-Lin Tsou ◽  
Ron P. Gladue ◽  
Laurie A. Carroll ◽  
Tim Paradis ◽  
James G. Boyd ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Human Monocytes ◽  
Normal Human Plasma ◽  
Transfected Cells ◽  
Downstream Signaling ◽  
Inflammatory Protein ◽  
Normal Human ◽  
High Concentrations ◽  
Macrophage Inflammatory Protein

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1α. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1α activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1α for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1α). Similarly, HCC-1 was less potent than MIP-1α in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was ∼100-fold lower than that of MIP-1α (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.

scholarly journals Macrophage Inflammatory Protein 3α Is Involved in the Constitutive Trafficking of Epidermal Langerhans Cells

1999 ◽  
Vol 190 (12) ◽  
pp. 1755-1768 ◽  
Author(s):  
Anne-Sophie Charbonnier ◽  
Norbert Kohrgruber ◽  
Ernst Kriehuber ◽  
Georg Stingl ◽  
Antal Rot ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Langerhans Cells ◽  
Chemokine Receptors ◽  
Tissue Response ◽  
Cc Chemokine ◽  
Clinically Normal ◽  
Receptor Repertoire ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Certain types of dendritic cells (DCs) appear in inflammatory lesions of various etiologies, whereas other DCs, e.g., Langerhans cells (LCs), populate peripheral organs constitutively. Until now, the molecular mechanism behind such differential behavior has not been elucidated. Here, we show that CD1a+ LC precursors respond selectively and specifically to the CC chemokine macrophage inflammatory protein (MIP)-3α. In contrast, CD14+ precursors of DC and monocytes are not attracted by MIP-3α. LCs lose the migratory responsiveness to MIP-3α during their maturation, and non-LC DCs do not acquire MIP-3α sensitivity. The notion that MIP-3α may be responsible for selective LC recruitment into the epidermis is further supported by the following observations: (a) MIP-3α is expressed by keratinocytes and venular endothelial cells in clinically normal appearing human skin; (b) LCs express CC chemokine receptor (CCR)6, the sole MIP-3α receptor both in situ and in vitro; and (c) non-LC DCs that are not found in normal epidermis lack CCR6. The mature forms of LCs and non-LC DCs display comparable sensitivity for MIP-3β, a CCR7 ligand, suggesting that DC subtype–specific chemokine responses are restricted to the committed precursor stage. Although LC precursors express primarily CCR6, non-LC DC precursors display a broad chemokine receptor repertoire. These findings reflect a scenario where the differential expression of chemokine receptors by two different subpopulations of DCs determines their functional behavior. One type, the LC, responds to MIP-3α and enters skin to screen the epidermis constitutively, whereas the other type, the “inflammatory” DC, migrates in response to a wide array of different chemokines and is involved in the amplification and modulation of the inflammatory tissue response.

scholarly journals Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Coombs ◽  
Antonios Georgantzoglou ◽  
Hazel A. Walker ◽  
Julian Patt ◽  
Nicole Merten ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Tissue Damage ◽  
Chemokine Receptors ◽  
Inflammatory Responses ◽  
Receptor Trafficking ◽  
Migratory Response ◽  
Cell Behaviors ◽  
Downstream Signaling

AbstractImmune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.

Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3α/CCL20 in human B cells

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2338-2345 ◽  
Author(s):  
Roman Krzysiek ◽  
Eric A. Lefevre ◽  
Jérôme Bernard ◽  
Arnaud Foussat ◽  
Pierre Galanaud ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Chemokine Receptor ◽  
Memory B Cells ◽  
Receptor Expression ◽  
B Cell Differentiation ◽  
Hematopoietic Stem ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Abstract The regulation of CCR6 (chemokine receptor 6) expression during B-cell ontogeny and antigen-driven B-cell differentiation was analyzed. None of the CD34+Lin− hematopoietic stem cell progenitors or the CD34+CD19+ (pro-B) or the CD19+CD10+ (pre-B/immature B cells) B-cell progenitors expressed CCR6. CCR6 is acquired when CD10 is lost and B-cell progeny matures, entering into the surface immunoglobulin D+ (sIgD+) mature B-cell pool. CCR6 is expressed by all bone marrow–, umbilical cord blood–, and peripheral blood–derived naive and/or memory B cells but is absent from germinal center (GC) B cells of secondary lymphoid organs. CCR6 is down-regulated after B-cell antigen receptor triggering and remains absent during differentiation into immunoglobulin-secreting plasma cells, whereas it is reacquired at the stage of post-GC memory B cells. Thus, within the B-cell compartment, CCR6 expression is restricted to functionally mature cells capable of responding to antigen challenge. In transmigration chemotactic assays, macrophage inflammatory protein (MIP)-3α/CC chemokine ligand 20 (CCL20) induced vigorous migration of B cells with differential chemotactic preference toward sIgD− memory B cells. These data suggest that restricted patterns of CCR6 expression and MIP-3α/CCL20 responsiveness are integral parts of the process of B-lineage maturation and antigen-driven B-cell differentiation.

scholarly journals MCP-1, not MIP-1α, Is the Endogenous Chemokine That Cooperates With TGF-β to Inhibit the Cycling of Primitive Normal but not Leukemic (CML) Progenitors in Long-Term Human Marrow Cultures

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2338-2344 ◽  
Author(s):  
J.D. Cashman ◽  
C.J. Eaves ◽  
A.H. Sarris ◽  
A.C. Eaves
Keyword(s):  
Inhibitory Activity ◽  
Neutralizing Antibodies ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Progenitor Cell Proliferation ◽  
Normal Human ◽  
Macrophage Inflammatory Protein

Abstract The long-term culture (LTC) system has been useful for analyzing mechanisms by which stromal cells regulate the proliferative activity of primitive normal, but not chronic myeloid leukemia (CML), hematopoietic progenitor cells. In previous studies, we identified two endogenous inhibitors in this system. One is transforming growth factor-β (TGF-β), which is equally active on primitive normal and CML progenitors. The other we now show to be monocyte chemoattractant protein-1 (MCP-1). Thus, MCP-1, when added to LTC, blocked the activation of primitive normal progenitors but did not arrest the cycling of primitive CML progenitors. Moreover, the endogenous inhibitory activity of LTC stromal layers could be overcome by the addition of neutralizing antibodies to MCP-1, but not to macrophage inflammatory protein-1α (MIP-1α). However, neither of these antibodies antagonized the inhibitory activity of NAc-Ser-Asp-Lys-Pro (AcSDKP) on primitive normal but not CML progenitor cycling in this system. Moreover, none of six other -C-C- or -C-X-C- chemokines, previously shown to inhibit primitive normal human CFC proliferation in semisolid assays, were found to act as negative regulators when added to normal LTC. These results provide further support for the concept that primitive CML progenitor cell proliferation is deregulated when these cells are exposed to limiting concentrations of multiple inhibitors, only some of which have differential actions on normal and Ph+/BCR-ABL+ cells.

scholarly journals Human Immunodeficiency Virus-1 Entry Into Purified Blood Dendritic Cells Through CC and CXC Chemokine Coreceptors

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1379-1386 ◽  
Author(s):  
Seyoum Ayehunie ◽  
Eduardo A. Garcia-Zepeda ◽  
James A. Hoxie ◽  
Richard Horuk ◽  
Thomas S. Kupper ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Rna Transcripts ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
Cxc Chemokine ◽  
Cc Chemokines

Abstract Blood dendritic cells (DC) are susceptible to both macrophage (M) and T-cell line (T) tropic human immunodeficiency virus type 1. The CC chemokines RANTES, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, eotaxin, and, to a lesser extent, monocyte chemoattractant protein-1 (MCP-1) and MCP-4 blocked entry of M-tropic virus into blood DC. The CXC chemokine, SDF-1, a fusin (CXCR4 chemokine receptor) ligand, and an antifusin antibody inhibited DC entry by T-tropic virus. Purified blood DC contained CCR1, CCR2, CCR3, and CCR5 as well as the CXCR4 chemokine receptor RNA transcripts and high levels of fusin on the cell surface. The coexpression of multiple chemokine receptors offers a molecular mechanism to explain the permissiveness of DC for both M- and T-tropic viruses.

scholarly journals Fcγ Receptor I- and III-Mediated Macrophage Inflammatory Protein 1α Induction in Primary Human and Murine Microglia

2002 ◽  
Vol 70 (9) ◽  
pp. 5177-5184 ◽  
Author(s):  
Xianyuan Song ◽  
Scott Shapiro ◽  
David L. Goldman ◽  
Arturo Casadevall ◽  
Matthew Scharff ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Pyrrolidine Dithiocarbamate ◽  
Wild Type ◽  
Human Microglia ◽  
Downstream Signaling ◽  
Inflammatory Protein ◽  
Α Chain ◽  
Macrophage Inflammatory Protein

ABSTRACT Microglial cell phagocytic receptors may play important roles in the pathogenesis and treatment of several neurological diseases. We studied microglial Fc receptor (FcR) activation with respect to the specific FcγR types involved and the downstream signaling events by using monoclonal antibody (MAb)-coated Cryptococcus neoformans immune complexes as the stimuli and macrophage inflammatory protein 1α (MIP-1α) production as the final outcome. C. neoformans complexed with murine immunoglobulin G (IgG) of γ1, γ2a, and γ3, but not γ2b isotype, was effective in inducing MIP-1α in human microglia. Since murine γ2b binds to human FcγRII (but not FcγRI or FcγRIII), these results indicate that FcγRI and/or FcγRIII is involved in MIP-1α production. Consistent with this, an antibody that blocks FcγRII (IV.3) failed to inhibit MIP-1α production, while an antibody that blocks FcγRIII (3G8) did. An anti-C. neoformans MAb, 18B7 (IgG1), but not its F(ab′)2, induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase kinase phosphorylation, and MIP-1α release was suppressed by the ERK inhibitor U0126. C. neoformans plus 18B7 also induced degradation of I-κBα, and MIP-1α release was suppressed by the antioxidant NF-κB inhibitor pyrrolidine dithiocarbamate. To confirm the role of FcR more directly, we isolated microglia from wild-type and various FcR-deficient mice and then challenged them with C. neoformans plus 18B7. While FcγRII-deficient microglia showed little difference from the wild-type microglia, both FcγRI α-chain- and FcγRIII α-chain-deficient microglia produced less MIP-1α, and the common Fc γ-chain-deficient microglia showed no MIP-1α release. Taken together, our results demonstrate a definitive role for FcγRI and FcγRIII in microglial chemokine induction and implicate ERK and NF-κB as the signaling components leading to MIP-1α expression. Our results delineate a new mechanism for microglial activation and may have implications for central nervous system inflammatory diseases.

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