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 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.
Ohkawara
Y
Y
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Lim
K G
KG
Xing
Z
Z
Glibetic
M
M
Nakano
K
K
Dolovich
J
J
Croitoru
K
K
Weller
P F
PF
Jordana
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D019013:CD40 Antigens / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D003432:Cross-Linking Reagents; D017931:DNA Primers / Q000235:genetics; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009298:Nasal Polyps / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D003432:Cross-Linking Reagents; D017931:DNA Primers; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor