The high-affinity IgE receptor (Fc epsilon RI) blocks apoptosis in normal human monocytes

Monocytes have a Limited life span, and their homeostasis is regulated by a poptosis in vivo. When cultured in the absence of appropriate exogenous sti muli, 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 (Fc epsilon RI) on human m onocytes from nonatopic individuals markedly reduces apoptosis induced by s erum deprivation or by CD95/Fas ligation. Aggregation of Fc epsilon RI redu ces its own expression but fails to modulate CD95/Fas expression. In contra st, Fc epsilon RI Ligation enhances the expression of the antiapoptotic mol ecules Bcl-2 and Bcl-xL, but not Mcl-1, in monocytes. Incubation of unstimu lated cells with culture supernatants of Fc epsilon RI-activated monocytes prolongs their Life span, whereas CD95/Fas expression remains unaffected. T he incidence of apoptosis is restored considerably when the supernatant is depleted of TNF-alpha, whereas elimination of IL-1 beta, GM-CSF, or IL-12 h as no effect. These results indicate that Fc epsilon RI mediates signals pr eventing monocyte apoptosis directly by increasing the levels of Bcl-2 and Bcl-xL, and indirectly by means of TNF-alpha in an autocrine and paracrine fashion. This process may contribute to the establishment of chronic allerg ic disorders such as atopic dermatitis.