title: The high-affinity IgE receptor (FcepsilonRI) 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 (FcepsilonRI) on human monocytes from nonatopic individuals markedly reduces apoptosis induced by serum deprivation or by CD95/Fas ligation. Aggregation of FcepsilonRI reduces its own expression but fails to modulate CD95/Fas expression. In contrast, FcepsilonRI 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 FcepsilonRI-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-alpha, whereas elimination of IL-1beta, GM-CSF, or IL-12 has no effect. These results indicate that FcepsilonRI mediates signals preventing 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 allergic disorders such as atopic dermatitis.
authors.affiliation: Department of Dermatology, Friedrich-Wilhelms-University, Bonn 53105, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Katoh
authors.forename: S
authors.initials: S
authors.lastname: Kraft
authors.forename: J H
authors.initials: JH
authors.lastname: Wessendorf
authors.forename: T
authors.initials: T
authors.lastname: Bieber
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011940:Receptor Aggregation / Q000187:drug effects; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051020:bcl-X Protein; D019014:fas Receptor / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; D003432:Cross-Linking Reagents; D016895:Culture Media, Serum-Free; D008070:Lipopolysaccharides; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D019014:fas Receptor; D007073:Immunoglobulin E