Selective down-regulation of high-affinity IgE receptor (FcepsilonRI) alpha-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 (FcepsilonRI)-mediated reactions. One million sensitized PB-derived MCs released 3.6 microg histamine, 215 pg IL-5, and 14 ng granulocyte macrophage-colony-stimulating factor (GM-CSF), whereas 10(6) sensitized CB-derived MCs released only 0.8 microg 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 FcepsilonRI 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 FcepsilonRI 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, FcepsilonRIalpha 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 FcepsilonRIalpha transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive.
Iida
M
M
Departments of Allergy and Immunology, National Children's Medical Research Center, Tokyo, Japan.
Matsumoto
K
K
Tomita
H
H
Nakajima
T
T
Akasawa
A
A
Ohtani
N Y
NY
Yoshida
N L
NL
Matsui
K
K
Nakada
A
A
Sugita
Y
Y
Shimizu
Y
Y
Wakahara
S
S
Nakao
T
T
Fujii
Y
Y
Ra
C
C
Saito
H
H
D000328:Adult; D000375:Aging / Q000235:genetics / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D015536:Down-Regulation / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006636:Histamine Release; D006801:Humans; D007231:Infant, Newborn; D015848:Interleukin-5 / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D016895:Culture Media, Serum-Free; D015848:Interleukin-5; D007476:Ionophores; D012333:RNA, Messenger; D017455:Receptors, IgE; D000001:Calcimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor