Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine
hematopoietic progenitors
F Salachas, E Schneider, FM Lemoine, B Lebel, M Daeron, S Navarro, H Ziltener and M Dy
CNRS URA 1461, Hopital Necker, Paris, France.
Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by
inducing histamine production. This effect does not result from
degranulation of histamine-containing cells, but from histamine synthesis,
as assessed by the following findings. (1) The histamine content of freshly
isolated bone marrow cells is too low to account for the increase in
extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine
production in the presence of the specific inhibitor of histidine
decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic
activity and the mRNA expression of HDC were enhanced in response to IL-3
or IgE. Artificial aggregation or formation of IgE immune complexes
augmented ther effect on histamine synthesis, indicating that the
aggregated form is responsible for this biologic activity. Yet, it is
apparently not mediated by Fc epsilon RI because their cross-linkage by
dinitrophenyl bovine serum albumin after presensitization with IgE did not
induce histamine production by hematopoietic progenitors. Among other
aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a
consistent but lower effect, whereas IgM and IgA were completely inactive.
The target cells of IL-3 and IgE in terms of histamine synthesis do not
belong to mature bone marrow populations, especially mast cells. They
copurify with hematopoietic progenitors in the low-density layers of a
discontinuous Ficoll gradient where they represent around 5% of the cells,
as determined by in situ hybridization. This percentage remained the same,
regardless of whether the cells were stimulated by IgE or IL-3 alone or by
a combination of both, suggesting a common responder cell. In accordance
with this notion, histamine-producing cells could not be distinguished from
each other on the basis of density, size and internal structure, or
rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the
induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect
of IgE.
Volume 84,
Issue 4,
pp. 1098-1107,
08/15/1994
Copyright © 1994 by The American Society of Hematology
