Liver-Expressed Chemokine/CC Chemokine Ligand 16 Attracts Eosinophils by Interacting with Histamine H4 Receptor

Nakayama, Takashi; Kato, Yoshiko; Hieshima, Kunio; Nagakubo, Daisuke; Kunori, Yuichi; Fujisawa, Takao; Yoshie, Osamu

doi:10.4049/jimmunol.173.3.2078

Cited by 68 publications

(47 citation statements)

References 28 publications

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“…H4R-induced chemotaxis or cytoskeletal changes have been described recently in other cell types such as eosinophils (43)(44)(45) and mast cells (38). A recent study also showed that the CC chemokine CCL-16 mediates chemotaxis via the H4R in eosinophils (46). Thus, histamine might play a role in the accumulation of DC and other cell types in allergic diseases such as atopic dermatitis or contact dermatitis.…”

Section: Discussionmentioning

confidence: 98%

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Gutzmer

Diestel

Mommert

et al. 2005

The Journal of Immunology

222

249

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There is increasing evidence that histamine as an important mediator of immediate type allergic reactions also effects professional APCs. Recent reports showed effects of histamine on human monocyte-derived dendritic cells (MoDC) mediated primarily via histamine H1 receptors (H1R) and H2R. We show here that MoDC also express H3R and H4R at the mRNA and protein level. mRNA of the H3R is down-regulated and mRNA of the H4R is up-regulated during the differentiation from monocytes to MoDC. H4R or H2R stimulation suppressed IL-12p70 production in MoDC. Induction of cAMP was necessary for IL-12p70 inhibition mediated via the H2R. In contrast, H4R stimulation did not affect cAMP production but induced the transcription factor AP-1, and U0126, an inhibitor of AP-1 transactivation and MEK, rescued H4R mediated IL-12p70 suppression. Moreover, MoDC responded to a H4R agonist (and also to a H2R agonist) with increased F-actin polymerization and migration in modified Boyden chamber assays, suggesting a chemotactic effect of histamine via the H2R and the H4R. Thus, H4R stimulation on MoDC results in immunomodulatory and chemotactic effects. Histamine induces chemotaxis and IL-12p70 suppression via different receptors using different signaling pathways, which might be important for the pathogenesis of and therapeutic interventions in allergic diseases.

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Section: Discussionmentioning

confidence: 98%

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Gutzmer

Diestel

Mommert

et al. 2005

The Journal of Immunology

222

249

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“…To test this possibility, we first generated stable transfectants of human D3 (L1.2-D3) or vector alone (L1.2-vector) using a murine L1.2 pre-B cell line (26). This cell line has been widely used to express cloned chemotactic receptors for the study of their functions (28) and, fortunately, did not express any dopamine receptors endogenously (data not shown). As shown in confirmed that dopamine-induced calcium mobilization in L1.2-D3 was suppressed by raclopride (an antagonist for D2 and D3), U-99194A (an antagonist for D3), and haloperidol (an antagonist for D2, D3, and D4), but not by SCH23390 (an antagonist for D1 and D5) or clozapine (an antagonist for D4) (1,29).…”

Section: Dopamine Induces Calcium Mobilization and Chemotaxis Via D3mentioning

confidence: 99%

“…This was conducted as described previously (28). In brief, cells were suspended at 10 6 cells/ml in HBSS containing 1 mg/ml BSA and 10 mM HEPES (pH 7.4), and loaded with 3 M Fura 2-AM fluorescence dye (Molecular Probes).…”

Section: Calcium Mobilization Assaymentioning

confidence: 99%

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Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

Watanabe

Nakayama

Nagakubo

et al. 2006

The Journal of Immunology

Self Cite

123

158

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The nervous systems affect immune functions by releasing neurohormones and neurotransmitters. A neurotransmitter dopamine signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. The secondary lymphoid tissues are highly innervated by sympathetic nerve fibers that store dopamine at high contents. Lymphocytes also produce dopamine. In this study, we examined expression and function of dopamine receptors in lymphocytes. We found that D3 was the predominant subtype of dopamine receptors in the secondary lymphoid tissues and selectively expressed by naive CD8+ T cells of both humans and mice. Dopamine induced calcium flux and chemotaxis in mouse L1.2 cells stably expressing human D3. These responses were almost completely inhibited by pertussis toxin, indicating that D3 was coupled with the Gαi class of G proteins. Consistently, dopamine selectively induced chemotactic responses in naive CD8+ T cells of both humans and mice in a manner sensitive to pertussis toxin and D3 antagonists. Dopamine was highly synergistic with CCL19, CCL21, and CXCL12 in induction of chemotaxis in naive CD8+ T cells. Dopamine selectively induced adhesion of naive CD8+ T cells to fibronectin and ICAM-1 through activation of integrins. Intraperitoneal injection of mice with dopamine selectively attracted naive CD8+ T cells into the peritoneal cavity. Treatment of mice with a D3 antagonist U-99194A selectively reduced homing of naive CD8+ T cells into lymph nodes. Collectively, naive CD8+ T cells selectively express D3 in both humans and mice, and dopamine plays a significant role in migration and homing of naive CD8+ T cells via D3.

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“…Moreover, human eosinophils have recently been shown not to express the histamine H 3 receptor. [48] Thus, histamine-induced human eosinophil apoptosis in the presence of IL-5 is unlikely to be mediated through the histamine H 3 receptor subtype.…”

Section: Discussionmentioning

confidence: 98%

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

Hasala¹,

Giembycz²,

Janka-Junttila³

et al. 2008

Pulmonary Pharmacology & Therapeutics

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A c c e p t e d m a n u s c r i p tCaspase activities were assessed by using commercial Caspase-Glo ® 3/7, 8, and 9 luminescence assays.Histamine (10-100 µM) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells.This effect was not mediated through any of the known histamine receptors or through nonspecific activation of 5-hydroxytryptamine receptors or α-adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general.In conclusion, the data presented herein indicate that histamine induces human eosinophil apoptosis in the presence of a survival-prolonging cytokine by a mechanism that does not apparently involve the activation of any of the currently known histamine receptor subtypes.The possibility exists that another, as yet unidentified, histamine receptor may exist in human eosinophils that regulates survival, although the participation of histamine receptorindependent mechanisms cannot be excluded. 3A c c e p t e d m a n u s c r i p t

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Liver-Expressed Chemokine/CC Chemokine Ligand 16 Attracts Eosinophils by Interacting with Histamine H4 Receptor

Cited by 68 publications

References 28 publications

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

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