Contrasting <i>in vitro</i> lymphocyte chemotactic activity of the hydroxyl enantiomers of 12‐hydroxy‐5,8,10,14‐eicosatetraenoic acid

Bacon, Kevin B.; Camp, R.D.R.; Cunningham, Fiona; Woollard, P.M.

doi:10.1111/j.1476-5381.1988.tb11727.x

Cited by 74 publications

(32 citation statements)

References 23 publications

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“…Chemotaxis Analysis-The migration of eosinophils was measured using a modified Boyden chamber with 5-m pore size polyvinylpyrrolidone-free filters (16).…”

Section: Methodsmentioning

confidence: 99%

Chemokine Receptor CCR3 Function Is Highly Dependent on Local pH and Ionic Strength

Dairaghi¹,

Oldham

Bacon³

et al. 1997

Journal of Biological Chemistry

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The CC chemokine receptor 3 (CCR3) plays an important role in the regulation of the migration of eosinophils, a leukocyte population involved in many inflammatory pathologies including asthma. CCR3 binds to the CC chemokine eotaxin, a promigratory cytokine originally isolated as the key component in a model of eosinophil-induced airway inflammation. We show here that eotaxin/CCR3 binding interactions exhibit a marked sensitivity to relatively small changes in the extracellular environment. In particular, modest variations in the pH and the level of sodium chloride over a range of physiologic and near physiologic conditions had dramatic effects on eotaxin binding and CCR3-mediated cytoplasmic Ca 2؉ mobilization. These biochemical indices were reflected at the functional level as well; small changes in pH and salt also resulted in striking changes in the migration of primary human eosinophils in vitro. These results reveal that relatively small perturbations in extracellular buffer conditions can yield widely disparate interpretations of CCR3 ligand binding and affinities and suggest that modulation of the tissue microenvironment might be utilized to control the affinity and efficacy of chemokine-mediated cell migration.Eosinophils are involved in many inflammatory pathologies including asthma, urticaria, and hypereosinophilic syndrome (1-3). The CC chemokine receptor 3 (CCR3) 1 and its ligands, most notably eotaxin, have been shown to play a central role in controlling eosinophil migration (4 -12). Eotaxin was originally isolated as a protein responsible for eosinophil chemoattraction in the bronchoalveolar fluid of allergen-sensitized guinea pigs (9). Subsequently, the human and mouse homologs were identified and also shown to be chemoattractants for eosinophils (10,12). Eotaxin has been shown to be a primary ligand for the seven-transmembrane G protein-coupled receptor CCR3. The genes for CCR3 and the related receptors CCR1-CCR5 are encoded within a 130-kilobase region of human chromosome 3 (13) indicating recent gene duplication and divergence and perhaps explaining the partial overlap of chemokine ligand repertoires. CCR3 is highly expressed on primary human eosinophils (50,000 -400,000 sites/cell) (5-7), consistent with the potent ability of eotaxin to selectively influence the migration of these cells.The mechanisms by which specific cells are attracted by specific chemokines have been a topic of intense interest and clinical relevance. The question is complicated by the fact that a number of closely related chemokine receptors with overlapping specificities are expressed on many different classes of leukocytes. In addition, the affinity of a specific receptor/ligand interaction can vary depending upon the specific cell type expressing the chemokine receptor, perhaps due to posttranslational modification events or G protein coupling. Thus it appears that cells can modulate their responses to chemokines, but how this is done is not yet clear. While most investigations have focused on factors intrinsic to the...

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“…Chemotaxis Analysis-The migration of eosinophils was measured using a modified Boyden chamber with 5-m pore size polyvinylpyrrolidone-free filters (16).…”

Section: Methodsmentioning

confidence: 99%

Chemokine Receptor CCR3 Function Is Highly Dependent on Local pH and Ionic Strength

Dairaghi¹,

Oldham

Bacon³

et al. 1997

Journal of Biological Chemistry

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“…Cell migration in response to XCP1 was evaluated using a modified chemotaxis microchamber technique as described (Bacon et al, 1988;Dieu et al, 1998). Briefly, 2 Â 10 5 COS-1 cells were transfected with either XCP1 expression plasmids, control vector plasmids or were mock-transfected.…”

Section: Chemotaxis Assaymentioning

confidence: 99%

Identification of murine and human XCP1 genes as C/EBP-ε-dependent members of FIZZ/Resistin gene family

et al. 2004

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“…Cell migration was evaluated using a chemotaxis microchamber technique (48-well Boyden microchamber; Neuroprobe, Pleasanton, CA) (38). Briefly, human recombinant CCL20 and CCL7 were diluted to 1 g/ml and 100 ng/ml in RPMI 1640 medium, respectively, and were added to the lower wells of the chemotaxis chamber.…”

Section: Chemotaxis Assaymentioning

confidence: 99%

IL-10 Induces CCR6 Expression During Langerhans Cell Development While IL-4 and IFN-γ Suppress It

Dieu-Nosjean

Massacrier²,

Vanbervliet³

et al. 2001

The Journal of Immunology

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Immune responses are initiated by dendritic cells (DC) that form a network comprising different populations. In particular, Langerhans cells (LC) appear as a unique population of cells colonizing epithelial surfaces. We have recently shown that macrophage-inflammatory protein-3α/CCL20, a chemokine secreted by epithelial cells, induces the selective migration of LC among DC populations. In this study, we investigated the effects of cytokines on the expression of the CCL20 receptor, CCR6, during differentiation of LC. We found that both IL-4 and IFN-γ blocked the expression of CCR6 and CCL20 responsiveness at different stages of LC development. The effect of IL-4 was reversible and most likely due to the transient blockade of LC differentiation. In contrast, IFN-γ-induced CCR6 loss was irreversible and was concomitant to the induction of DC maturation. When other cytokines involved in DC and T cell differentiation were tested, we found that IL-10, unlike IL-4 and IFN-γ, maintained CCR6 expression. The effect of IL-10 was reversible and upon IL-10 withdrawn, CCR6 was lost concomitantly to final LC differentiation. In addition, IL-10 induced the expression of CCR6 and responsiveness to CCL20 in differentiated monocytes that preserve their ability to differentiate into mature DC. Finally, TGF-β, which induces LC differentiation, did not alter early CCR6 expression, but triggered its irreversible down-regulation, in parallel to terminal LC differentiation. Taken together, these results suggest that the recruitment of LC at epithelial surface might be suppressed during Th1 and Th2 immune responses, and amplified during regulatory immune responses involving IL-10 and TGF-β.

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Contrasting in vitro lymphocyte chemotactic activity of the hydroxyl enantiomers of 12‐hydroxy‐5,8,10,14‐eicosatetraenoic acid

Cited by 74 publications

References 23 publications

Chemokine Receptor CCR3 Function Is Highly Dependent on Local pH and Ionic Strength

Chemokine Receptor CCR3 Function Is Highly Dependent on Local pH and Ionic Strength

Identification of murine and human XCP1 genes as C/EBP-ε-dependent members of FIZZ/Resistin gene family

IL-10 Induces CCR6 Expression During Langerhans Cell Development While IL-4 and IFN-γ Suppress It

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