Induction of the high-affinity IgE receptor (Fc epsilon RI) on human mast cells by IL-4.
The high-affinity IgE receptor (Fc epsilon RI) is necessary for the induction of IgE-mediated allergic reactions. Cross-linking of Fc epsilon RI expressed on mast cells causes the release of various inflammatory mediators, which trigger allergic reactions. Recently, mast cells lacking Fc epsilon RI have been observed in vivo and in vitro, suggesting the presence of regulational mechanisms in the induction of Fc epsilon RI. In this report, we demonstrate that IL-4 up-regulates Fc epsilon RI in cultured human mast cells, which are grown from cord blood mononuclear cells in the presence of stem cell factor and IL-6, and usually lack Fc epsilon RI expression. At the protein level, the induction of Fc epsilon RI was observed by flow cytometric analysis and the induced Fc epsilon RI expression was stable for at least 23 days in the presence of IL-4. Consistently, Northern blot analysis demonstrated the increase of alpha chain mRNA of Fc epsilon RI and revealed that the up-regulation of Fc epsilon RI occurred at the transcriptional level. Fc epsilon RI induced by IL-4 was functional and caused histamine and beta-hexosaminidase release from mast cells upon cross-linking. Taken together, these results indicate a new role of IL-4 in allergic reactions, besides the stimulation of IgE production.
Toru
H
H
Department of Pediatrics, School of Medicine, Tokyo Medical and Dental University, Japan.
Ra
C
C
Nonoyama
S
S
Suzuki
K
K
Yata
J
J
Nakahata
T
T
D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006636:Histamine Release; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics; D019089:Stem Cell Factor / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D015850:Interleukin-6; D017455:Receptors, IgE; D019089:Stem Cell Factor; D015847:Interleukin-4; D001619:beta-N-Acetylhexosaminidases