Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia

García‐Zepeda, Eduardo A.; Rothenberg, Marc E.; Ownbey, Robert T.; Celestin, Jocelyn; Leder, Philip; Luster, Andrew D.

doi:10.1038/nm0496-449

Cited by 646 publications

(442 citation statements)

References 33 publications

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“…10C). Eotaxin is well recognized as a potent chemoattractant for eosinophils (46,47). Although eosinophil accumulation was not compared in WT versus Tbx21 2/2 mice, it has previously been reported that Ghanian pediatric patients with CM had uniformly low eosinophil counts because of tissue sequestration and destruction rather than decreased production during acute illness followed by eosinophilia 30 d after cure (48).…”

Section: Figurementioning

confidence: 99%

The Transcription Factor T-bet Regulates Parasitemia and Promotes Pathogenesis duringPlasmodium bergheiANKA Murine Malaria

Oakley

Sahu

Lotspeich-Cole

et al. 2013

The Journal of Immunology

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The pathogenesis of experimental cerebral malaria (ECM) is an immunologic process, mediated in part by Th1 CD4+ T cells. However, the role of the Th1 CD4+ T cell differentiation program on the ability to control parasitemia and susceptibility to ECM disease during blood stage malaria has never been assessed directly. Using the Plasmodium berghei ANKA murine model of ECM and mice deficient for the transcription factor T-bet (the master regulator of Th1 cells) on the susceptible C57BL/6 background, we demonstrate that although T-bet plays a role in the regulation of parasite burden, it also promotes the pathogenesis of ECM. T-bet−deficient (Tbx21−/−) mice had higher parasitemia than wild type controls did during the ECM phase of disease (17.7 ± 3.1% versus 10.9 ± 1.5%). In addition, although 100% (10/10) of wild type mice developed ECM by day 9 after infection, only 30% (3/10) of Tbx21−/− mice succumbed to disease during the cerebral phase of infection. Resistance to ECM in Tbx21−/− mice was associated with diminished numbers of IFN-γ–producing CD4+ T cells in the spleen and a lower accumulation of CD4+ and CD8+ T cells in the brain. An augmented Th2 immune response characterized by enhanced production of activated GATA-3+ CD4+ T cells and elevated levels of the eotaxin, MCP-1, and G-CSF cytokines was observed in the absence of T-bet. Our results suggest that in virulent malarias, immune modulation or therapy resulting in an early shift toward a Th2 response may help to ameliorate the most severe consequences of malaria immunopathogenesis and the prospect of host survival.

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Section: Figurementioning

confidence: 99%

The Transcription Factor T-bet Regulates Parasitemia and Promotes Pathogenesis duringPlasmodium bergheiANKA Murine Malaria

Oakley

Sahu

Lotspeich-Cole

et al. 2013

The Journal of Immunology

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“…Tumour infiltrating eosinophils may also modulate angiogenesis and desmoplastic reaction (Ono et al, 1997;Samoszuk, 1997). Eotaxin is the most researched C-C chemokine (Fankin et al, 2000), its human gene has been characterized and shown to be an early response gene of cytokine-stimulated epithelial and endothelial cells (Garcia-Zepeda et al, 1996). It may provide the molecular basis for eosinophil recruitment in certain tumours especially of the gastrointestinal tract.…”

Section: Clinicalmentioning

confidence: 99%

Influence of pathological tumour variables on long-term survival in resectable gastric cancer

2002

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Although tumour stage and nodal status are established prognostic factors for resectable gastric cancer, the relative importance of other pathological characteristics remains unclear. This study reports univariate and multivariate analyses of the prognostic value of various pathological and staging factors based on 324 patients entered into the MRC randomised surgical trial for gastric cancer. In the univariate analysis tumour stage, nodal status, UICC clinical stage, number of involved nodes, WHO predominant type, mixed Lauren type, Ming type, tumour differentiation, lymphocytic and tumour stromal eosinophilic infiltration were all found to have a significant impact on survival (logrank test, 5% level). In the multivariate analysis, UICC clinical stage and eosinophilic infiltration were found to have a significant influence. Risk of death increased for UICC stage II and III patients (Hazard Ratio for stage II compared to stage I=2.0, 95% Confidence Interval (CI) 1.4 -2.9; Hazard Ratio for stage III compared to stage I=3.5, 95% CI 2.5 -4.8). Patients with numerous eosinophils had a lower risk of death than those with none (Hazard Ratio=0.5, 95% CI 0.3 -0.8). This association between survival and eosinophilic infiltration merits further study.

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“…Eotaxin/CCL11 is a member of the CC chemokine family that has potent chemotactic activity for eosinophils (15,16), basophils (17), mast cells (18), and Th2-type lymphocytes (19). Eotaxin/ CCL11 protein is up-regulated in a variety of inflammatory diseases possessing an eosinophilic component, such as allergic asthma (20,21), chronic sinusitis (22), and allergic rhinitis (23), and is thought to be a key player in the pathogenesis of these conditions.…”

mentioning

confidence: 99%

Eotaxin/CCL11 Suppresses IL-8/CXCL8 Secretion from Human Dermal Microvascular Endothelial Cells

Lukacs

Kunkel

2002

The Journal of Immunology

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The CC chemokine eotaxin/CCL11 is known to bind to the receptor CCR3 on eosinophils and Th2-type lymphocytes. In this study, we demonstrate that CCR3 is expressed on a subpopulation of primary human dermal microvascular endothelial cells and is up-regulated by TNF-α. We found that incubation of human dermal microvascular endothelial cells with recombinant eotaxin/CCL11 suppresses TNF-α-induced production of the neutrophil-specific chemokine IL-8/CXCL8. The eotaxin/CCL11-suppressive effect on endothelial cells was not seen on IL-1β-induced IL-8/CXCL8 release. Eotaxin/CCL11 showed no effect on TNF-α-induced up-regulation of growth-related oncogene-α or IFN-γ-inducible protein-10, two other CXC chemokines tested, and did not affect production of the CC chemokines monocyte chemoattractant protein-1/CCL2 and RANTES/CCL5, or the adhesion molecules ICAM-1 and E-selectin. These results suggest that eotaxin/CXCL11 is not effecting a general suppression of TNF-αR levels or signal transduction. Suppression of IL-8/CXCL8 was abrogated in the presence of anti-CCR3 mAb, pertussis toxin, and wortmannin, indicating it was mediated by the CCR3 receptor, Gi proteins, and phosphatidylinositol 3-kinase signaling. Eotaxin/CCL11 decreased steady state levels of IL-8/CXCL8 mRNA in TNF-α-stimulated cells, an effect mediated in part by an acceleration of IL-8 mRNA decay. Eotaxin/CCL11 may down-regulate production of the neutrophil chemoattractant IL-8/CXCL8 by endothelial cells in vivo, acting as a negative regulator of neutrophil recruitment. This may play an important biological role in the prevention of overzealous inflammatory responses, aiding in the resolution of acute inflammation or transition from neutrophilic to mononuclear/eosinophilic inflammation.

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Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia

Cited by 646 publications

References 33 publications

The Transcription Factor T-bet Regulates Parasitemia and Promotes Pathogenesis duringPlasmodium bergheiANKA Murine Malaria

The Transcription Factor T-bet Regulates Parasitemia and Promotes Pathogenesis duringPlasmodium bergheiANKA Murine Malaria

Influence of pathological tumour variables on long-term survival in resectable gastric cancer

Eotaxin/CCL11 Suppresses IL-8/CXCL8 Secretion from Human Dermal Microvascular Endothelial Cells

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