Intracellular localization and release of eotaxin from normal eosinophils

Nakajima, Toshiharu; Yamada, Hirokazu; Iikura, Motoyasu; Miyamasu, Misato; Izumi, Satoshi; Shida, Hisato; Ohta, Ken; Imai, Toshio; Yoshie, Osamu; Mochizuki, Mitsuru; Schröder, Jens‐M.; Morita, Yutaka; Yamamoto, Kazuhiko; Hirai, Koichi

doi:10.1016/s0014-5793(98)00863-1

Cited by 72 publications

(47 citation statements)

References 43 publications

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“…Eosinophils are now recognized to contain preformed stores of diverse cytokines and chemokines within their cytoplasmic granules (22). Thus, in addition to their distinctive cationic proteins, eosinophil granules contain chemokines (e.g., eotaxin (23) and RANTES (24,25)) and cytokines with disparate and potentially opposing activities, notably including the prototypical Th2 cytokine IL-4 (26 -28) and the Th1 cytokine IL-12 (29 -31). The regulated release of these preformed cytokines occurs not by exocytotic fusion of granules with the plasma membranes to extrude all granule contents, but rather by selective processes based on vesicular mobilization and transport of these granule-derived cytokines (32)(33)(34).…”

Section: Nterleukin-16 Is a Cytokine Initially Identified As A Chemmentioning

confidence: 99%

“…These findings suggested that actions of IL-16 to enhance LTC 4 and IL-4 release from eosinophils might be mediated by endogenous CCR3-acting chemokines. Eosinophils contain two chemokines, eotaxin and RANTES, that act via CCR3 and are stored preformed within eosinophil granules (23)(24)(25). We have shown that both RANTES and eotaxin induce lipid body formation, prime for enhanced LTC 4 production (35), and elicit vesicular transport-mediated IL-4 release (43) from eosinophils via CCR3 activation.…”

Section: Involvement Of G Protein-coupled Ccr3 Activation In Il-16-inmentioning

confidence: 99%

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IL-16 Promotes Leukotriene C4 and IL-4 Release from Human Eosinophils via CD4- and Autocrine CCR3-Chemokine-Mediated Signaling

Bandeira‐Melo

Sugiyama

Woods

et al. 2002

The Journal of Immunology

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Human eosinophils are potential sources of inflammatory and immunomodulatory mediators, including cysteinyl leukotrienes, chemokines, and cytokines, which are pertinent to allergic inflammation. We evaluated the means by which IL-16, a recognized eosinophil chemoattractant, might act on eosinophils to affect their capacity to release leukotriene C4 (LTC4) or their preformed stores of chemokines (eotaxin, RANTES) or Th1 (IL-12) or Th2 (IL-4) cytokines. IL-16 dose dependently (0.01–100 nM) elicited new lipid body formation, intracellular LTC4 formation at lipid bodies, and priming for enhanced calcium ionophore-activated LTC4 release. IL-16 also elicited brefeldin A-inhibitable, vesicular transport-mediated release of preformed IL-4, but not IL-12, from eosinophils. CD4 is a recognized IL-16R, and accordingly anti-CD4 Fab, soluble CD4, and a CD4 domain 4-based IL-16 blocking peptide inhibited the actions of IL-16 on eosinophils. Although CD4 is not G-protein coupled, pertussis toxin inhibited IL-16-induced eosinophil activation. IL-16 actions were found to be mediated by the autocrine activity, not of platelet-activating factor, but rather of endogenous CCR3-acting chemokines. IL-16 induced the rapid vesicular transport-mediated release of RANTES. The effects of IL-16 were blocked by CCR3 inhibitors (met-RANTES, anti-CCR3 mAb) and by neutralizing anti-eotaxin and anti-RANTES mAbs, but not by platelet-activating factor receptor antagonists (CV6209, BN52021). RANTES and eotaxin each enhanced LTC4 and IL-4 (but not IL-12) release. Therefore, IL-16 activation of eosinophils is CD4-mediated to elicit the extracellular release of preformed RANTES and eotaxin, which then in an autocrine fashion act on plasma membrane CCR3 receptors to stimulate both enhanced LTC4 production and the preferential release of IL-4, but not IL-12, from within eosinophils.

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Section: Nterleukin-16 Is a Cytokine Initially Identified As A Chemmentioning

confidence: 99%

Section: Involvement Of G Protein-coupled Ccr3 Activation In Il-16-inmentioning

confidence: 99%

IL-16 Promotes Leukotriene C4 and IL-4 Release from Human Eosinophils via CD4- and Autocrine CCR3-Chemokine-Mediated Signaling

Bandeira‐Melo

Sugiyama

Woods

et al. 2002

The Journal of Immunology

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“…22) Notable mRNA expression of eotaxin-2/CCL24, but no mRNA expression of eotaxin-1/CCL11 and eotaxin-3/CCL26 was observed in the cells treated with ATRA or ATRAϩIL-5 on day 2 ( Fig. 2A), with no mRNA expression on day 1 and day 3 as well (data not shown).…”

Section: Differentiation Of Ht93 Cells To An Eosinophilicmentioning

confidence: 87%

“…The same cells were stimulated with complement component, C5a (100 ng/ml) in the presence of cytochalasin B (5 mg/ml) (as shown in the ref. 22) and the eotaxin-2/CCL24 production was estimated. The production was minimally enhanced (approx.…”

Section: E (Nϭ3) (D) Expression Of Gata-1 Protein Was Detected In Tmentioning

confidence: 99%

Production and Regulation of Eotaxin-2/CCL24 in a Differentiated Human Leukemic Cell Line, HT93

Yoshida¹,

Aizu-Yokota²,

Sonoda³

et al. 2007

Biological & Pharmaceutical Bulletin

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When a human leukemic cell line, HT93 was incubated with all-trans retinoic acid (ATRA), IL-5, or both, this cell line was differentiated into eosinophic lineage, in that an eosinophilic specific granule proteins, major basic protein (MBP) and eosinophil peroxidase (EPO) appeared. Both CD11b and CC chemokine receptor, CCR3 expression were upregulated, while CD71 expression was downregulated by ATRA or ATRA؉IL-5. Concomitantly, marked production of eotaxin-2/CCL24 was observed, but no production of eotaxin-1/CCL11 and eotaxin-3/CCL26 was detected. Since only 20 to 30% cells incubated with ATRA became positive for CCR3, CCR3؉ population was enriched by a magnetic activated cell sorter (MACS). Enriched CCR3 ؉ population produced higher eotaxin-2/CCL24 than the CCR3 ؊ population, indicating that differentiated eosinophils are capable of producing eotaxin-2/CCL24. During the ATRA-induced differentiation, expression of a transcriptional factor, GATA-1 was significantly increased. Introduction of siRNA against GATA-1 markedly reduced the ATRAinduced differentiation markers including CD11b and CCR3, as well as reduced eotaxin-2/CCL24 production. Finally, ATRA-induced differentiation and eotaxin-2/CCL24 production were greatly enhanced in the GATA-1-overexpressed clones. These results indicate that the ability to produce eotaxin-2/CCL24 is acquired during the differentiation into eosinophilic lineage which is dependent on GATA-1 expression.

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“…Studies in guinea pigs , Humbles et al 1997) and man (Lamkhioued et al 1997, Mattoli et al 1997, Ying et al 1997, Nakajima et al 1998, using in situ hybridisation and immunohistochemistry, show that the major sources of Eotaxin-1 are inflammatory cells such as macrophages, as well as eosinophils themselves, and also airway smooth muscle cells, vascular endothelial cells and, in particular, airway epithelial cells. Two Th2 cytokines, IL-4 and IL-13, have been shown to act synergistically with TNFα to induce Eotaxin-1 production in human cells in culture , Terada et al 2000.…”

Section: Regulation Of Chemokine Production By Th2 Cytokinesmentioning

confidence: 99%