Utilizing Fcε-Bak chimeric protein for studying IgE-FcεRI interactions

Ruth Belostotsky, Haya Lorberboum-Galski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

We previously constructed a pro-apoptotic Fcε-Bak chimeric protein, targeted against cells expressing the IgE high affinity receptor (FcεRI). We demonstrated that the chimeric protein is internalized by target mast cells and kills them. These results, which constitute a promising basis for applying this approach to antiallergic therapy, raise some theoretical questions with respect to two major issues: (a) is the monomeric Fcε-Bak-FcεRI complex able to undergo endocytosis, and (b) does the receptor binding domain of human IgE (Fcε) react with rodent FcεRI? In an attempt to answer these questions, we have now thoroughly investigate the interaction of human (h) and mouse (m) Fcε-Bak with FcεRI-positive cells. Using established cultures of rodent and human origin, as well as a primary mouse mast cell culture, we demonstrate that binding of the chimeric protein to the membrane is followed by quick endocytosis, leading to the apoptosis of specific cells. We also confirm that this interaction depends on FcεRI and not on other IgE receptors. We found that the effect of Fcε-Bak on the cells depends on the level of surface FcεRI expression, but not on the origin of the target cells or of the Fcε moiety. We suggest that endocytosis of the monomeric Fcε-Bak-FcεRI complex results from the inability of Fcε-Bak to transduce signals, characteristic of the monomeric IgE-FcεRI complex due to the absence of the variable portion of the IgE molecule. Our results also indicate that at least the Fcε fragment of human IgE is able to interact with both human and rodent FcεRI.

Original languageEnglish
Pages (from-to)89-99
Number of pages11
JournalClinical Immunology
Volume110
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Antiallergic drugs
  • Apoptosis
  • Chimeric proteins
  • FcεRI
  • Mast cells/basophils

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