CD40 EXPRESSION BY HUMAN PERIPHERAL-BLOOD EOSINOPHILS

In this study, we have investigated CD40 expression in human periphera l blood eosinophils and in human chronically inflamed nasal tissues, i .e., nasal polyps. We show by both reverse transcriptase-PCR and North ern blot analysis that eosinophils from allergic subjects express huma n CD40 mRNA, We also show that constitutive CD40 mRNA expression in eo sinophils could be upregulated by exposure to IgA immune complexes and downregulated by IL-10 and the synthetic steroid budesonide. In addit ion, we demonstrate that eosinophils express CD40 protein by flow cyto metry, Such expression is biologically functional as cross-linking CD4 0 with CD40 mAbs enhances eosinophil survival in a dose-dependent fash ion; in addition, CD40 ligation stimulates eosinophils to release GM-C SF, CD40-mediated eosinophil survival was largely inhibited by an anti -GM-CSF neutralizing antibody suggesting GM-CSF involvement in the sur vival enhancing mechanism, CD40 mRNA was also detected in total RNA ex tracted from nasal polyp tissues but not in RNA isolated from normal n asal mucosa (inferior turbinate); by immunohistochemistry, we were abl e to detect immunoreactive CD40 protein in a variety of cell types in the polyp stroma, but primarily in eosinophils, These observations sug gest previously unforeseen interactions between eosinophils and cells expressing the CD40 ligand and, thus, novel pathways by which eosinoph ils may contribute to the regulation of airway inflammation.