Abstract
When mast cells are activated through their immunoglobulin (Ig)E receptors, release of low molecular weight mediators like histamine is followed by secretion of multiple cytokines, including interleukin (IL)-3, IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor. Here we report that stimulated mast cells also synthesize IL-13 mRNA and protein; secretion of this cytokine may be of particular importance because of its ability to stimulate IgE expression. IL-13 transcripts detected by a semiquantitative reverse transcriptase-mediated polymerase chain reaction assay were induced within 30 min after stimulation of mast cells by dinitrophenyl plus monoclonal IgE anti-dinitrophenyl, and peaked at about 1 h. Within 3 h of IgE stimulation, secreted IL-13 bioactivity, estimated by proliferation of an IL-13-dependent cell line, reached levels equivalent to 1-2 ng/ml of IL-13. When added to human B lymphocytes, the mast cell-derived IL-13 activity (like bone fide IL-13) induced Ig C epsilon transcripts, DNA recombination characteristic of the isotype switch to C epsilon, and the secretion of IgE protein. These results suggest a model of local positive feedback interactions between mast cells and B cells, which could play a role in the pathogenesis of atopy.
MeSH Terms
Animals
Antigens, CD/immunology
Antigens, Differentiation, B-Lymphocyte/immunology
B-Lymphocytes/immunology
Base Sequence
Basophils/drug effects,metabolism
Bone Marrow Cells
CD40 Antigens
Calcimycin/pharmacology
Cell Line
Gene Expression Regulation
Gene Rearrangement, B-Lymphocyte
Humans
Immunoglobulin Class Switching
Immunoglobulin E/biosynthesis,genetics
Interleukin-13/biosynthesis,genetics,metabolism
Interleukin-4/biosynthesis,genetics
Mast Cells/drug effects,immunology,metabolism
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Polymerase Chain Reaction
RNA, Messenger/biosynthesis
Receptors, IgE/immunology
Tetradecanoylphorbol Acetate/pharmacology
Tumor Necrosis Factor-alpha/biosynthesis,genetics
Chemicals
Antigens, CD
Antigens, Differentiation, B-Lymphocyte
CD40 Antigens
Interleukin-13
RNA, Messenger
Receptors, IgE
Tumor Necrosis Factor-alpha
Interleukin-4
Immunoglobulin E
Calcimycin
Tetradecanoylphorbol Acetate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Burd P R
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20592, USA.
Thompson W C
Max E E
Mills F C
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