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PMID: 7535336 Published · ppublish English Journal Article

Activated mast cells produce interleukin 13.

The Journal of experimental medicine ·Vol. 181 ·No. 4 ·1995-04-01 ·Pages 1373-80

Burd PR, Thompson WC, Max EE, Mills FC

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
References (31)
31 references, click to expand
  1. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization.
    J Immunol. 1980 Jun;124(6):2728-37 PMID: 7373045
  2. Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor.
    Nat Genet. 1994 Jun;7(2):125-9 PMID: 7920628
  3. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor.
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):9175-9 PMID: 3321069
  4. Establishment of an immature mast cell line from a patient with mast cell leukemia.
    Leuk Res. 1988;12(4):345-55 PMID: 3131594
  5. The IL-4 gene maps to chromosome 11, near the gene encoding IL-3.
    J Immunol. 1988 Nov 1;141(9):3067-71 PMID: 2902144
  6. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes.
    J Immunol. 1989 Jan 15;142(2):679-87 PMID: 2521353
  7. Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice.
    Oncogene Res. 1988;2(2):149-65 PMID: 2851124
  8. Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores.
    Nature. 1989 May 4;339(6219):64-7 PMID: 2469965
  9. Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin.
    J Cell Physiol. 1989 Aug;140(2):323-34 PMID: 2663885
  10. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines.
    J Exp Med. 1989 Jul 1;170(1):245-57 PMID: 2473161
  11. IgE secretion by Epstein-Barr virus-infected purified human B lymphocytes is stimulated by interleukin 4 and suppressed by interferon gamma.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5580-4 PMID: 2546158
  12. New insights into "the riddle of the mast cells": microenvironmental regulation of mast cell development and phenotypic heterogeneity.
    Lab Invest. 1990 Jan;62(1):5-33 PMID: 2404155
  13. Clustering of cytokine genes on mouse chromosome 11.
    J Exp Med. 1990 Apr 1;171(4):1301-14 PMID: 1969921
  14. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin.
    Nature. 1990 Jul 19;346(6281):274-6 PMID: 2374592
  15. Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha.
    J Clin Invest. 1991 Feb;87(2):446-53 PMID: 1991831
  16. Mast cells as a source of multifunctional cytokines.
    Immunol Today. 1990 Dec;11(12):458-64 PMID: 2073318
  17. Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses.
    J Exp Med. 1991 Jul 1;174(1):103-7 PMID: 1829107
  18. Modulation of IL-4 induced germline epsilon RNA synthesis in human B cells by tumor necrosis factor-alpha, anti-CD40 monoclonal antibodies or transforming growth factor-beta correlates with levels of IgE production.
    Int Immunol. 1992 Mar;4(3):397-406 PMID: 1373645
  19. Ig mu-epsilon isotype switch in IL-4-treated human B lymphoblastoid cells. Evidence for a sequential switch.
    J Immunol. 1992 Aug 1;149(3):1075-85 PMID: 1321850
  20. New concepts about the mast cell.
    N Engl J Med. 1993 Jan 28;328(4):257-65 PMID: 8418407
  21. Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3735-9 PMID: 8097324
  22. Polymerase chain reaction-based mRNA quantification using an internal standard: analysis of oncogene expression.
    Methods Enzymol. 1993;218:446-73 PMID: 7685470
  23. Structural comparison and chromosomal localization of the human and mouse IL-13 genes.
    J Immunol. 1993 Jun 15;150(12):5436-44 PMID: 8099936
  24. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10.
    J Immunol. 1993 Dec 1;151(11):6370-81 PMID: 7902377
  25. Modulation of murine macrophage function by IL-13.
    J Immunol. 1993 Dec 15;151(12):7151-60 PMID: 7903102
  26. Interleukin 13 is a B cell stimulating factor.
    J Exp Med. 1994 Jan 1;179(1):135-43 PMID: 7903680
  27. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells.
    Immunol Today. 1994 Jan;15(1):19-26 PMID: 7907877
  28. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations.
    Science. 1994 May 20;264(5162):1152-6 PMID: 8178175
  29. Independent regulation of DNA recombination and immunoglobulin (Ig) secretion during isotype switching to IgG1 and IgE.
    J Exp Med. 1994 Jun 1;179(6):1877-83 PMID: 8195714
  30. Interleukin 13: novel role in direct regulation of proliferation and differentiation of primitive hematopoietic progenitor cells.
    J Exp Med. 1994 Jul 1;180(1):75-82 PMID: 7516418
  31. A new leukemia cell line with Philadelphia chromosome characterized as basophil precursors.
    Leuk Res. 1985;9(3):381-90 PMID: 3858609
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1995-04-01
Pages
1373-80
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191950
Subset
IM
Databases
GENBANK
J00222, L06081, L13028, M32599, M99403, X01677, X05253, X56795, Y00467
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