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Blood, 15 February 2001, Vol. 97, No. 4, pp. 1016-1022

IMMUNOBIOLOGY

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

Makoto Iida, Kenji Matsumoto, Hisashi Tomita, Toshiharu Nakajima, Akira Akasawa, Noriko Yuyama Ohtani, Ning Lu Yoshida, Keiko Matsui, Akiko Nakada, Yuji Sugita, Yuji Shimizu, Shunichi Wakahara, Toru Nakao, Yasuyuki Fujii, Chisei Ra, and Hirohisa Saito

From the Departments of Allergy and Immunology, National Children's Medical Research Center, Tokyo; Genox Research, Kanagawa; Department of Medicine, Gunma University School of Medicine, Gunma; Molecular and Cellular Biology Group, Medical Research Laboratories, and the Ethical Business Strategy Division, Taisho Pharmaceutical, Saitama; and Allergy Research Center, Juntendo University School of Medicine, Tokyo, Japan.

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 (Fcepsilon RI)-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 Fcepsilon RI alpha  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 Fcepsilon RI alpha  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, Fcepsilon RIalpha 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 Fcepsilon RIalpha transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive.

© 2001 by The American Society of Hematology.
 

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