Evidence for glycosylphosphatidylinositol (GPI)‐anchored eosinophil‐derived neurotoxin (EDN) on human granulocytes

Debierre‐Grockiego, Françoise; Desaint, Corinne; Fuentes, Vincent; Poussin, Mathilde; Socié, Gèrard; Azzouz, Nahid; Schwarz, Ralph Τ.; Prin, Lionel; Gouilleux-Gruart, Valérie

doi:10.1016/s0014-5793(03)00106-6

Cited by 5 publications

(5 citation statements)

References 36 publications

(37 reference statements)

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“…It can be synthesized as a secretory molecule present in neutrophil granules or as a GPI-anchored form at the cellular membrane (30). During this study, we observed that LTB 4 stimulation at a physiological concentration leads to neutrophil secretion of EDN in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 74%

“…Eosinophil-derived neurotoxin, a member of the RNase gene family (27), is predominantly expressed in human eosinophils but is also detected in neutrophil cell lysate (28,29). Moreover, a GPI-anchored form of eosinophil-derived neurotoxin (EDN) has been detected on the surface of human neutrophils (30). EDN has known antiviral activities against respiratory viruses such as respiratory syncytial virus group B (31) and its related rodent counterpart, pneumonia virus of mice (32).…”

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confidence: 99%

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Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Gaudreault

Gosselin

2008

The Journal of Immunology

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Leukotriene B4 (LTB4) is a lipid mediator of inflammation that was recently shown to exert antiviral activities. In this study, we demonstrate that the release of antimicrobial proteins by neutrophils contribute to an early host defense against influenza virus infection in vitro as well as in vivo. Daily i.v. treatments with LTB4 lead to a significant decrease in lung viral loads at day 5 postinfection in mice infected with influenza A virus compared with the placebo-treated group. This reduction in viral load was not present in mice deficient in the high-affinity LTB4 receptor. Viral clearance in lungs was associated with up-regulated presence of antimicrobial peptides such as β-defensin-3, members of the mouse eosinophil-related RNase family, and the mouse cathelicidin-related antimicrobial peptide. Our results also indicate that neutrophils are important in the antiviral effect of LTB4. Viral loads in neutrophil-depleted mice were not diminished by LTB4 administration, and a substantial reduction in the presence of murine cathelicidin-related antimicrobial peptide and the murine eosinophil-related RNase family in lung tissue was observed. Moreover, in vitro treatment of human neutrophil cultures with LTB4 led rapidly to the secretion of the human cathelicidin LL-37 and eosinophil-derived neurotoxin, known as antiviral peptides. Pretreatment of cell cultures with specific LTB4 receptor antagonists clearly demonstrate the implication of the high-affinity LTB4 receptor in the LTB4-mediated activity. Together, these results demonstrate the importance of neutrophils and the secretion of antimicrobial peptides during the early immune response mediated by LTB4 against a viral pathogen.

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Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Gaudreault

Gosselin

2008

The Journal of Immunology

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“…Selection of mAb 3.252 was based on surface reactivity of mammary lavage (MAL) eosinophils, although the reactive protein was subsequently shown (by flow cytometry) to be present both on the cell surface and intracellularly. It is not uncommon for intracellular molecules to also be detected on the surface of cells, as has been shown to be the case with eosinophil derived neurotoxin (EDN), previously considered to be intracellular but recently identified at low levels on the surface of eosinophils [ 16 ]. The exclusive reactivity of mAb 3.252 at comparable levels on all eosinophils at different tissue sites suggests that this mAb would be suitable as a diagnostic tool for the discrimination of eosinophils in sheep.…”

Section: Discussionmentioning

confidence: 99%

Production of monoclonal antibodies reactive with ovine eosinophils

Sansome¹,

Young

Meeusen

et al. 2007

BMC Immunol

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Background: There is strong evidence implicating eosinophils in host defence against parasites as well as allergic disease pathologies. However, a lack of reagents such as monoclonal antibodies (mAbs) specific for eosinophils has made it difficult to confirm the functional role of eosinophils in such disease conditions. Using an established mammary model of allergic inflammation in sheep, large numbers of inflammatory cells enriched for eosinophils were collected from parasitestimulated mammary glands and used for the generation of mAbs against ovine eosinophils.

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“…Eosinophil-derived neurotoxin is a cationic eosinophil protein [4] belonging to the RNase A superfamily [18]. Since eosinophils and Fig.…”

Section: Discussionmentioning

confidence: 99%

“…2 Expression pattern of genes with significantly different expression shown in ratio values for MS patients with acute relapse before IVMP therapy versus healthy controls (a) and MS controls (b). Abbreviations: LCK; T-cell-specific protein tyrosine kinase, TCF7; T-cellspecific transcription factor 7, ISGF3G; Interferon-stimulated gene factor 3 gamma subunit, EDN; Eosinophil-derived neurotoxin their secretory ribonucleases are apparently somehow responsible for the immune response in viral infections [4,18], this result could mean that EDN expression rises in response to a viral infection in MS exacerbation. On the other hand, topical steroids increase human eosinophil killing by enhancing apoptosis at clinically relevant drug concentrations [22].…”

Section: Discussionmentioning

confidence: 99%

Suppression of immune system genes by methylprednisolone in exacerbations of multiple sclerosis

et al. 2004

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Acute relapses of multiple sclerosis (MS) are treated with intravenous methylprednisolone (IVMP), which speeds recovery from exacerbation. It is known that IVMP suppresses the immunological activation which occurs during an acute attack of MS. However, the specific target genes affected by this therapy remain obscure. A cDNA microarray for 448 genes was used to identify the target genes in IVMP therapy. Total RNA was isolated from peripheral blood mononuclear cells derived from six MS patients immediately before and after completion of therapy. IVMP significantly reduced mRNA levels for T-cell-specific transcription factor 7 (p=0.02), T-cell-specific protein-tyrosine kinase (p=0.02), T-cell surface glycoprotein CD5 (p=0.05) and interferon-stimulated gene factor 3 gamma subunit (p=0.04). Significantly increased expression was found for eosinophil-derived neurotoxin (p=0.05). The suppression of expression of genes associated with T-cell differentiation and antigen-specific T-cell activation detected in this study may contribute to the beneficial effect of MP in relapses of MS.

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Evidence for glycosylphosphatidylinositol (GPI)‐anchored eosinophil‐derived neurotoxin (EDN) on human granulocytes

Cited by 5 publications

References 36 publications

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Production of monoclonal antibodies reactive with ovine eosinophils

Suppression of immune system genes by methylprednisolone in exacerbations of multiple sclerosis

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