Abstract
Substantial numbers of human mast cells (MCs) were generated from umbilical cord blood (CB) and from adult peripheral blood (PB). A single CB progenitor produced 15 436 MCs, whereas a single PB progenitor produced 807 MCs on average. However, PB-derived MCs were far more active than CB-derived MCs in terms of high-affinity IgE receptor (FcεRI)-mediated reactions. One million sensitized PB-derived MCs released 3.6 μg histamine, 215 pg IL-5, and 14 ng granulocyte macrophage–colony-stimulating factor (GM-CSF), whereas 106 sensitized CB-derived MCs released only 0.8 μg histamine, 31 pg IL-5, and 0.58 ng GM-CSF on anti-IgE challenge. However, ionophore A23 187 released similar levels of histamine from the 2 MC types. PB-derived MCs highly expressed surface FcεRI α chain, and CB-derived MCs almost lacked it in the absence of IgE. PB-derived MCs expressed approximately 5 times higher levels of messenger RNA (mRNA) for FcεRI α chain than CB-derived MCs, but mRNAs for β and γ chains of the receptors were equally expressed. Among the approximately 5600 kinds of full-length human genes examined by using the high-density oligonucleotide probe-array system, FcεRIα was ranked the fifth most increased transcript in PB-derived MCs. The 4 other increased transcripts were unrelated to MC function. These results suggest that IgE-mediated reactions may be restricted during early infancy through the selective inhibition of FcεRIα transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive.
Molecular Mechanisms for Transcriptional Regulation of Human High-Affinity IgE Receptor β-Chain Gene Induced by GM-CSF
