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IgE-independent interleukin-4 expression and induction of a late phase of
leukotriene C4 formation in human blood basophils
B Ochensberger, S Rihs, T Brunner and CA Dahinden
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.
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.
Volume 86,
Issue 11,
pp. 4039-4049,
12/01/1995
Copyright © 1995 by The American Society of Hematology
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