CD40 expression by human peripheral blood eosinophils

In this study, we have investigated CD40 expression in human peripheral blood eosinophils and in human chronically inflamed nasal tissues, i.e., nasal polyps. We show by both reverse transcriptase-PCR and Northern blot analysis that eosinophils from allergic subjects express human CD40 mRNA. We also...

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Bibliographic Details
Published in:The Journal of clinical investigation 1996-04, Vol.97 (7), p.1761-1766
Main Authors: Ohkawara, Y, Lim, K G, Xing, Z, Glibetic, M, Nakano, K, Dolovich, J, Croitoru, K, Weller, P F, Jordana, M
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - pharmacology
Base Sequence
CD40 Antigens - blood
CD40 Antigens - chemistry
CD40 Antigens - genetics
Cross-Linking Reagents
DNA Primers - genetics
Eosinophils - immunology
Eosinophils - metabolism
Gene Expression
Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors
Granulocyte-Macrophage Colony-Stimulating Factor - immunology
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Humans
Immunohistochemistry
Inflammation - genetics
Inflammation - immunology
Molecular Sequence Data
Nasal Polyps - genetics
Nasal Polyps - immunology
Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary:In this study, we have investigated CD40 expression in human peripheral blood eosinophils and in human chronically inflamed nasal tissues, i.e., nasal polyps. We show by both reverse transcriptase-PCR and Northern blot analysis that eosinophils from allergic subjects express human CD40 mRNA. We also show that constitutive CD40 mRNA expression in eosinophils could be upregulated by exposure to IgA immune complexes and downregulated by IL-10 and the synthetic steroid budesonide. In addition, we demonstrate that eosinophils express CD40 protein by flow cytometry. Such expression is biologically functional as cross-linking CD40 with CD40 mAbs enhances eosinophil survival in a dose-dependent fashion; in addition, CD40 ligation stimulates eosinophils to release GM-CSF. CD40-mediated eosinophil survival was largely inhibited by an anti-GM-CSF neutralizing antibody suggesting GM-CSF involvement in the survival enhancing mechanism. CD40 mRNA was also detected in total RNA extracted from nasal polyp tissues but not in RNA isolated from normal nasal mucosa (inferior turbinate); by immunohistochemistry, we were able to detect immunoreactive CD40 protein in a variety of cell types in the polyp stroma, but primarily in eosinophils. These observations suggest previously unforeseen interactions between eosinophils and cells expressing the CD40 ligand and, thus, novel pathways by which eosinophils may contribute to the regulation of airway inflammation.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci118603