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IgE-independent interleukin-4 expression and induction of a late phase of leukotriene C4 formation in human blood basophils

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1995

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Ochensberger, Brigitte
Rihs, Silvia
Dahinden, Clemens A.

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Blood. 1995, 86(11), pp. 4039-4049. ISSN 0006-4971. eISSN 1528-0020

Zusammenfassung

T-helper cells can differentiate into at least two subtypes secreting distinct profiles of cytokines, Th1 and Th2, regulating immunoprotection and different immunopathologies. Interleukin-4 (IL-4) is both the product and the inducer of Th2 cells, raising the question whether IL-4 can be produced in response to antigen-independent stimuli. Here we show that human basophils produce IL-4 on stimulation with IL-3 and C5a or C5adesarg in similar amounts as induced by IgE- receptor-cross-linking. C5a-induced IL-4 production requires the presence of IL-3, with little effect of the sequence of stimuli addition. No “Th1-cytokines” (interferon-gamma and IL-2) and even no “Th2-cytokines” (IL-3, IL-5, IL-10, and granulocyte-macrophage colony- stimulating factor) are produced by basophils in response to either IgE- dependent or IgE-independent activation. The generation of leukotriene C4 (LTC4) is regulated in a similar manner. However, C5a induces a rapid, transient burst of leukotriene formation only if added after IL- 3. Interestingly, upon prolonged culture, a late phase of continuous LTC4 production is observed, which also requires two signals (IL-3 and C5a), but rather depends on their continuous presence than on their sequence of action. These data describe an antigen-independent pathway of very restricted IL-4 expression. Thus, basophils must be considered as central immunoregulatory cells of the innate immune system. Furthermore, the results show that LTC4 can also be generated more continuously for many hours, a phenomenon that may be of particular importance in chornic allergic inflammation, such as asthma.

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570 Biowissenschaften, Biologie

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ISO 690OCHENSBERGER, Brigitte, Silvia RIHS, Thomas BRUNNER, Clemens A. DAHINDEN, 1995. IgE-independent interleukin-4 expression and induction of a late phase of leukotriene C4 formation in human blood basophils. In: Blood. 1995, 86(11), pp. 4039-4049. ISSN 0006-4971. eISSN 1528-0020
BibTex
@article{Ochensberger1995IgEin-14317,
  year={1995},
  title={IgE-independent interleukin-4 expression and induction of a late phase of leukotriene C4 formation in human blood basophils},
  number={11},
  volume={86},
  issn={0006-4971},
  journal={Blood},
  pages={4039--4049},
  author={Ochensberger, Brigitte and Rihs, Silvia and Brunner, Thomas and Dahinden, Clemens A.}
}
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    <dcterms:abstract xml:lang="eng">T-helper cells can differentiate into at least two subtypes secreting distinct profiles of cytokines, Th1 and Th2, regulating immunoprotection and different immunopathologies. Interleukin-4 (IL-4) is both the product and the inducer of Th2 cells, raising the question whether IL-4 can be produced in response to antigen-independent stimuli. Here we show that human basophils produce IL-4 on stimulation with IL-3 and C5a or C5adesarg in similar amounts as induced by IgE- receptor-cross-linking. C5a-induced IL-4 production requires the presence of IL-3, with little effect of the sequence of stimuli addition. No “Th1-cytokines” (interferon-gamma and IL-2) and even no “Th2-cytokines” (IL-3, IL-5, IL-10, and granulocyte-macrophage colony- stimulating factor) are produced by basophils in response to either IgE- dependent or IgE-independent activation. The generation of leukotriene C4 (LTC4) is regulated in a similar manner. However, C5a induces a rapid, transient burst of leukotriene formation only if added after IL- 3. Interestingly, upon prolonged culture, a late phase of continuous LTC4 production is observed, which also requires two signals (IL-3 and C5a), but rather depends on their continuous presence than on their sequence of action. These data describe an antigen-independent pathway of very restricted IL-4 expression. Thus, basophils must be considered as central immunoregulatory cells of the innate immune system. Furthermore, the results show that LTC4 can also be generated more continuously for many hours, a phenomenon that may be of particular importance in chornic allergic inflammation, such as asthma.</dcterms:abstract>
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