CD40 expression by human peripheral blood eosinophils.

Abstract

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,

CD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation

“…1,6,7 Despite their important role in the pathophysiology of allergy, the precise mechanisms by which eosinophils escape spontaneous apoptosis in allergic disorders have not been completely elucidated. In the present study we confirmed a previous report by Ohkawara et al 16 that eosinophils may express CD40 and that CD40 activation delays eosinophil apoptosis as potently as GM-CSF stimulation. We also demonstrated that CD40 mediates enhancement of eosinophil survival at least partly through induction of C-IAP2 expression and provided in vivo evidence that CD40-mediated C-IAP2 expression occurs in eosinophils at the site of allergic inflammation.…”

“…16,19,20 Blood eosinophils and neutrophils have been cultured in the presence of these compounds for 24 or 48 hours before being assayed for CD40 expression to determine whether they affect CD40 expression in granulocytes. Neither IFN-γ (10 µg/mL), GM-CSF (500 U/mL), nor IgA-Ic induced CD40 expression in neutrophils, as determined by means of immunoblotting (Fig 1, A) and flow cytometry (data not shown).…”

“…A few years ago, Ohkawara et al 16 reported that eosinophils isolated from the blood or tissue of allergic subjects express CD40 and that CD40 stimulation results in enhanced survival of cultured blood eosinophils. These findings suggest that CD40 ligation, like IL-5, IL-3, and GM-CSF stimulation, might enhance eosinophil survival in allergic disorders and therefore participate in the development of eosinophilia.…”

A Role for CD40-CD40 Ligand Interactions in the Generation of Type 1 Cytokine Responses in Human Leprosy

“…In addition, IL-10 was shown to down-regulate CD40 mRNA synthesis in eosinophils (4). Because Th1 cytokines such as IFN-␥ are prominent in tuberculoid lesions, and Th2 cytokines such as IL-10 are predominant in lepromatous lesions (34, 3.…”

“…CD40 is a 50-kDa glycoprotein present on the surface of B cells (1), monocytes (2), dendritic cells (3), eosinophils (4), and endothelial cells (5) and is a member of the TNF receptor superfamily (6,7). The expression of CD40 on monocytes has been shown to be up-regulated by IFN-␥, GM-CSF, and IL-3 (2).…”