The high-affinity IgE receptor (FcεRI) blocks apoptosis in normal human monocytes
Norito Katoh, … , Jörg H.M. Weßendorf, Thomas Bieber
Norito Katoh, … , Jörg H.M. Weßendorf, Thomas Bieber
Published January 15, 2000
Citation Information: J Clin Invest. 2000;105(2):183-190. https://doi.org/10.1172/JCI6895.
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Article

The high-affinity IgE receptor (FcεRI) blocks apoptosis in normal human monocytes

Abstract

Monocytes have a limited life span, and their homeostasis is regulated by apoptosis in vivo. When cultured in the absence of appropriate exogenous stimuli, they undergo apoptosis, but under the influence of survival signals, these cells differentiate into macrophages or dendritic cells. Here we show that ligation of the high-affinity IgE receptor (FcεRI) on human monocytes from nonatopic individuals markedly reduces apoptosis induced by serum deprivation or by CD95/Fas ligation. Aggregation of FcεRI reduces its own expression but fails to modulate CD95/Fas expression. In contrast, FcεRI ligation enhances the expression of the antiapoptotic molecules Bcl-2 and Bcl-xL, but not Mcl-1, in monocytes. Incubation of unstimulated cells with culture supernatants of FcεRI-activated monocytes prolongs their life span, whereas CD95/Fas expression remains unaffected. The incidence of apoptosis is restored considerably when the supernatant is depleted of TNF-α, whereas elimination of IL-1β, GM-CSF, or IL-12 has no effect. These results indicate that FcεRI mediates signals preventing monocyte apoptosis directly by increasing the levels of Bcl-2 and Bcl-xL, and indirectly by means of TNF-α in an autocrine and paracrine fashion. This process may contribute to the establishment of chronic allergic disorders such as atopic dermatitis.

Authors

Norito Katoh, Stefan Kraft, Jörg H.M. Weßendorf, Thomas Bieber

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Ligation of FcεRI leads to its downregulation. Monocytes were either unt...
Ligation of FcεRI leads to its downregulation. Monocytes were either untreated (nil) or incubated for 1 hour with either anti-IgG (aIgG), anti-IgM (aIgM), or with IgE followed by anti-IgE (aIgE), washed, and then cultured in the presence of serum. After 24 hours, the receptor expression was monitored by flow cytometry using an anti-FcεRI–specific mAb that does not interact with the IgE-binding site. Note the spontaneous decrease of the FcεRI expression during the culture time further accelerated by receptor ligation. Similar results were obtained in the absence of serum. Data are expressed as the mean ± SD of data from 3 experiments.