‘Reverse gear’ cellular movement mediated by chemokines

Zlatopolskiy, Andrey; Laurence, Jeffrey

doi:10.1046/j.1440-1711.2001.01015.x

Cited by 28 publications

(20 citation statements)

References 33 publications

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“…28,42 Different from our observation in monocytes, which almost exclusively exhibit reverse migration in response to eotaxin-3, T lymphocytes respond in a biphasic mode to the CXCR4 ligand SDF-1; although attracted by low concentrations of SDF-1, the cells get repulsed at high SDF-1 concentrations. In this system, both effects are attributed to the chemokine receptor CXCR4 and evidence for different underlying signal transduction mechanisms at low and high stimulus concentrations has been provided.…”

Section: Discussioncontrasting

confidence: 70%

Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes

Ogilvie

Paoletti

Clark‐Lewis

et al. 2003

Blood

101

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Eotaxin-3 (CCL26) belongs to the group of CC chemokines that attract eosinophils, basophils, and Th2 lymphocytes. Like eotaxin (CCL11) and eotaxin-2 (CCL24), eotaxin-3 mediates its activity through CCR3. Here we show that eotaxin-3 also binds to CCR2 on monocytes and CCR2-transfected cells. In contrast to monocyte chemotactic protein 1 (MCP-1; CCL2), eotaxin-3 does not trigger intracellular calcium mobilization, enzyme release, or phosphorylation of the mitogenactivated protein (MAP) kinase ERK and induces a weak chemotaxis in monocytes. Instead, eotaxin-3 inhibits MCP-1-mediated responses, thus acting as a natural antagonist for CCR2. This study also demonstrates that eotaxin-3 promotes active movement of monocytes away from a gradient of eotaxin-3 in vitro. This repellent effect is amplified when an additional gradient of MCP-1 is applied, demonstrating that the 2 mechanisms are synergistic. Eotaxin-3 effects on monocytes are largely abolished when cells are pretreated with MCP-1 or CCR2 antagonists. Like MCP-1-mediated migration, repulsion is sensitive to Bordetella pertussis toxin, indicating the involvement of G i protein-coupled receptors. However, using transfected cells expressing CCR2 we could not detect F-actin formation or an active movement away induced by eotaxin-3, suggesting that either expression of a single receptor type is not sufficient to mediate cell repulsion or that the used transfected cell lines lack additional interaction molecules that are required for reverse migration. Eotaxin-3 was expressed by vascular endothelial cells and was essential for endothelial transmigration of eosinophils. Our data provide a mechanism by which 2 chemokine gradients that are oriented in opposite directions could cooperate in efficiently driving out monocytes from blood vessels into tissue. IntroductionLike eotaxin (CCL11) and eotaxin-2 (CCL24), eotaxin-3 (CCL26) has been reported as a selective stimulus for eosinophilic granulocytes by interacting with the chemokine receptor CCR3. [1][2][3][4] This receptor is highly expressed on eosinophils, basophils, and Th2 lymphocytes, [5][6][7][8][9] and is therefore involved mainly in allergic inflammation. 10,11 CCR3-recruiting chemokines and monocyte chemotactic protein 1 (MCP-1) were found to be expressed in several tissues, especially in pathologic reactions, in which Th2-type cytokines are produced. [12][13][14][15][16] In addition to eosinophils, basophils, and Th2 lymphocytes, which are typically found in allergic inflammations and express CCR3, these infiltrates also contain monocytes that lack CCR3. 17 Eotaxin-3 is expressed in vascular endothelial cells and dermal fibroblasts after interleukin 4 (IL-4) and 18,19 and in bronchial tissue on allergen challenge. 20,21 In a current report, its relevance for transendothelial migration of eosinophils has been elucidated, 22 whereas the significance of the constitutive expression in the reproductive system and the heart 2 remains to be clarified. Eotaxin-3 is as efficient as eotaxin in attracting eosinophils and...

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Section: Discussioncontrasting

confidence: 70%

Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes

Ogilvie

Paoletti

Clark‐Lewis

et al. 2003

Blood

101

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“…These two migratory mechanisms have been described for other chemokines and other leukocyte types (30,38,39). However, until now, in sharp contrast to the pDC response to CXCR3Ls, the chemokine-induced haptotaxis and chemorepulsion were shown to take place separately from each other and only as alternatives to also viable chemotaxis.…”

Section: Discussionmentioning

confidence: 86%

Plasmacytoid Dendritic Cell Recruitment by Immobilized CXCR3 Ligands

Kohrgruber

Gröger

Meraner

et al. 2004

The Journal of Immunology

109

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Plasmacytoid dendritic cells (pDCs) recognize microbes, viruses in particular, and provide unique means of innate defense against them. The mechanism of pDC tissue recruitment remained enigmatic because the ligands of CXCR3, the cardinal chemokine receptor on pDCs, have failed to induce in vitro chemotaxis of pDCs in the absence of additional chemokines. In this study, we demonstrate that CXCR3 is sufficient to induce pDC migration, however, by a migratory mechanism that amalgamates the features of haptotaxis and chemorepulsion. To mediate “haptorepulsion” of pDCs, CXCR3 requires the encounter of its cognate ligands immobilized, optimally by heparan sulfate, in a form of a negative gradient. This is the first report of the absolute requirement of chemokine immobilization and presentation for its in vitro promigratory activity. The paradigmatic example of pDC haptorepulsion described here may represent a new pathophysiologically relevant migratory mechanism potentially used by other cells in response to other chemokines.

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“…This can be paralleled to what happens in MCH neurons of the lateral hypothalamus, where SDF-1a also exerts opposite effects on the action potential discharge depending on the concentration (Guyon et al 2005b). Moreover, this can also be observed in other contexts, for example, low levels of SDF-1 (!100 ng/ml) are attractive, whereas higher levels (O1 mg/ml) are repulsive for T cells (Zlatopolskiy & Laurence 2001). Several putative mechanisms for these opposite effects, which are not mutually exclusive, are reviewed in Fig.…”

Section: Effects On Neuronal Activity and Neurotransmitter Releasementioning

confidence: 99%

Multiple actions of the chemokine stromal cell-derived factor-1α on neuronal activity

Guyon¹,

Nahon²

2007

Journal of Molecular Endocrinology

118

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The chemokine SDF-1a and its cognate receptor CXCR4 are expressed in several neuronal populations. This review focuses on our current knowledge about the actions of this chemokine on neuronal excitability, through CXCR4 or other yet unknown pathways. In various neuronal populations (CA1 neurons of the hippocampus, granular and Purkinje cells of the cerebellum, melanin-concentrating hormone neurons of the lateral hypothalamus, vasopressinergic neurons of the supraoptic and the paraventricular nucleus of the hypothalamus, and dopaminergic neurons of the substantia nigra), SDF-1a can modulate the activity of neurons by multiple regulatory pathways including and often combining: (i) modulation of voltage-dependent channels (sodium, potassium, and calcium), (ii) activation of the G-protein-activated inward rectifier potassium current, and (iii) increase in neurotransmitter release (gamma-amino butyric acid (GABA), glutamate, and dopamine), often through Ca-dependent mechanisms. The possible mechanisms underlying these effects and their consequences in terms of modulation of neuroendocrine systems and physiopathology are discussed.

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‘Reverse gear’ cellular movement mediated by chemokines

Cited by 28 publications

References 33 publications

Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes

Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes

Plasmacytoid Dendritic Cell Recruitment by Immobilized CXCR3 Ligands

Multiple actions of the chemokine stromal cell-derived factor-1α on neuronal activity

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