Selective down-regulation of high-affinity IgE receptor (FcεRI) α-chain messenger RNA among transcriptome in cord blood-derived versus adult peripheral blood-derived cultured human mast cells

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 (Fc epsilon RI)-mediated reactions. One million sensitized PB-derived MCs released 3.6 mug histamine, 215 pg IL-5, and 14 ng granulocyte macrophage-colony-stimulating factor (GMCSF), whereas 10(6) sensitized CB-derived MCs released only 0.8 mug 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. PR-derived MCs highly expressed surface FceRI alpha chain, and CB-derived MCs almost lacked it in the absence of IgE, PR-derived MCs expressed approximately 5 times higher levels of messenger RNA (mRNA) for Fc epsilon RI a chain than CB-derived MCs, but mRNAs for beta and gamma 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, Fc epsilon RI alpha 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 Fc epsilon RI alpha transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive. (C) 2001 by The American Society of Hematology.