RANTES- and interleukin-8-induced responses in normal human eosinophils: effects of priming with interleukin-5

Schweizer, RC; Welmers, BA; Ja, Raaijmakers; Zanen, P; Lammers, J.-W. J.; Koenderman, Leo

doi:10.1182/blood.v83.12.3697.bloodjournal83123697

Cited by 12 publications

(1 citation statement)

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“…Results of another study in vitro of cytokine‐induced eosinophil transendothelial cell migration showed that Rantes alone induced the migration of eosinophils across an endothelial cell barrier, and that this action was maximized by pretreatment of the eosinophils with IL5 (25). Rantes also induces mild activation of eosinophils in vitro, as measured by the release of cationic protein, superoxide production, and the induction of hypodensity (26). Interleukin‐5 is a potent chemoattractant for eosinophis and an activator of eosinophil functions (27).…”

Section: Discussionmentioning

confidence: 99%

In Situ Rantes and Interferon‐γ Gene Expression in Pediatric Small Bowel Crohn's Disease

Berrebi,

Banerjee,

Paris

et al. 1997

J. pediatr. gastroenterol. nutr.

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BackgroundRantes (regulated upon activation, normal T cell expressed and secreted) is a chemotactic cytokine for memory T lymphocytes, monocytes, and eosinophils. The cytokine interferon‐γ (IFN‐γ) plays a key in the immune response. Their distributions and possible roles in the selective accumulation of inflammatory cells in Crohn's disease (CD) were examined by determining the expression of Rantes and IFN‐γ genes in patients with CD using in situ hybridization (ISH) on frozen and paraffin‐embedded tissue sections.MethodsIntestinal and mesenteric lymph node samples from 9 children who had undergone ileal resection for CD were examined for the presence of epithelioid‐giant cell granulomas (EGCG) and Rantes and IFN‐γ messenger RNA (mRNA). Normal pediatric intestine (n = 5) and lymph nodes (n = 2) served as controls.ResultsMany cells in all CD specimens in the epithelial compartment, lamina propria, and the EGCG gave positive signal with the Rantes antisense probe. Labelled cells were identified on paraffin sections as lymphocytes, macrophages, and epithelioid cells. There were Rantes‐positive cells in the control intestinal tissues, but many Rantes‐positive cells in control lymph nodes that showed follicular hyperplasia. IFN‐γ‐positive cells were present in all CD ileal and lymph node specimens, predominantly in close contact with EGCC. No positive signal was obtained with the Rantes and IFN‐γ sense control probes.ConclusionsThese findings suggest that Rantes and IFN‐γ contribute to the selective accumulation of macrophages and memory T helper lymphocytes inside the granulomas and inflammatory infiltrates that are characteristic of CD.

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Section: Discussionmentioning

confidence: 99%

In Situ Rantes and Interferon‐γ Gene Expression in Pediatric Small Bowel Crohn's Disease

Berrebi,

Banerjee,

Paris

et al. 1997

J. pediatr. gastroenterol. nutr.

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Analysis of Signal Transduction Pathways in Human Eosinophils Activated by Chemoattractants and the T-Helper 2–Derived Cytokines Interleukin-4 and Interleukin-5

Coffer¹,

Schweizer²,

Dubois³

et al. 1998

Blood

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Activation and recruitment of eosinophils in allergic inflammation is in part mediated by chemoattractants and T-helper 2 (Th2)-derived cytokines. However, little is known concerning the signal transduction mechanisms by which this activation occurs. We have investigated tyrosine kinase-mediated activation of phosphatidylinositol 3-kinase (PI3K) and compared this with the activation of the p21ras-ERK signaling pathway in human eosinophils. The related cytokines interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF), all induced PI3K activity detected in antiphosphotyrosine immunoprecipitates. Furthermore, the chemoattractants platelet-activating factor (PAF), RANTES, and C5a were also able to induce phosphotyrosine-associated PI3K activity. Protein kinase B (PKB) is a downstream target of PI3K activation by growth factors. Induction of PKB phosphorylation in human eosinophils was transiently induced on activation with the cytokines IL-4 and IL-5, as well as the chemoattractants PAF, C5a, and RANTES showing a broad activation profile. Surprisingly, analysis of the activation of the mitogen-activated protein (MAP) kinases p44ERK1 and p42ERK2, showed that ERK2, but not ERK1, was transiently activated in human eosinophils after stimulation with IL-5 or PAF. Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Finally, using specific inhibitors of both the p21ras-ERK and PI3K signaling pathways, a role was demonstrated for PI3K, but not p21ras-ERK, in activation of the serum-treated zymosan (STZ)-mediated respiratory burst in IL-5 and PAF-primed eosinophils. In summary, these data show that in human eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP kinase signal transduction pathways with distinct functional consequences showing complex regulation of eosinophil effector functions.

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Analysis of Signal Transduction Pathways Regulating Cytokine-Mediated Fc Receptor Activation on Human Eosinophils

Bracke¹,

Coffer²,

Lammers³

et al. 1998

The Journal of Immunology

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Igs can be potent stimulants of eosinophil activation since interaction with IgA or IgG-coated particles can lead to eosinophil degranulation. We have investigated the comparative roles of mitogen-activated protein (MAP) kinases (MAPKs; ERK1/2 and p38) and phosphatidylinositol-3 kinase (PI3K) in the priming and regulation of Fc receptor functioning on human eosinophils utilizing a MAPK kinase (MEK) inhibitor (PD98059), a p38 inhibitor SB203580, and the widely used PI3K inhibitors wortmannin and LY294002. We demonstrate that priming of human eosinophils with Th2-derived cytokines, IL-4 and IL-5, differentially activate phosphotyrosine-associated PI3K and ERK and p38 MAP kinases. This activation can be inhibited by pre-incubation with wortmannin or LY294002, PD98059, and SB203580, respectively. Analysis of the effects of the inhibitors on rosette formation between human eosinophils and IgA- or IgG-coated beads revealed that activation of MEK was not required for IgA binding after priming with IL-4 or IL-5. However, inhibition of MEK did inhibit IL-5-primed binding of IgG-beads. The rosette formation of primed eosinophils with IgA-beads could be completely inhibited by wortmannin and LY294002 treatment, demonstrating a critical role for PI3K. Interestingly, inhibition of the p38 pathway also resulted in a complete blockade of IgA rosette formation. This work demonstrates regulatory control by inside-out signaling of Fc receptors by various cytokines on human eosinophils. Thus in vivo the local production of Th2-derived cytokines will regulate the effector functions of Fc receptors.

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RANTES- and interleukin-8-induced responses in normal human eosinophils: effects of priming with interleukin-5

Cited by 12 publications

References 0 publications

In Situ Rantes and Interferon‐γ Gene Expression in Pediatric Small Bowel Crohn's Disease

In Situ Rantes and Interferon‐γ Gene Expression in Pediatric Small Bowel Crohn's Disease

Analysis of Signal Transduction Pathways in Human Eosinophils Activated by Chemoattractants and the T-Helper 2–Derived Cytokines Interleukin-4 and Interleukin-5

Analysis of Signal Transduction Pathways Regulating Cytokine-Mediated Fc Receptor Activation on Human Eosinophils

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